All Numbered Sessions Listing

Tuesday, October 16

4:15 PM–5:00 PM

1. ASHG Welcome and Presidential Address: Who Are We?

Hall C, Ground Level, San Diego Convention Center

As ASHG turns 70 years old, it is once again time to assess the Society’s values, mission, and plans. Over the year, the ASHG Board of Directors and staff sent a survey to the membership to study the landscape of human genetics to strengthen current activities and to help anticipate new areas for the Society’s attention. In his address, Nelson will review early results from these efforts, provide historical context from research into human origins and from the journeys of ASHG’s founders, and offer a longer term vision that emphasizes the value of ASHG for helping the public understand the consequences and limitations of our research.

 


Tuesday, October 16

5:00 PM–5:15 PM

2. ASHG Victor A. McKusick Leadership Award Presentation and Lecture: Rare Variation of Genes and Genomes - Disease Traits, Clan Genomics, and Clinical Genomics: Insights into Disease Biology and Human Evolution

Hall C, Ground Level, San Diego Convention Center

The ASHG Victor A. McKusick Leadership Award recognizes individuals whose professional achievements have fostered and enriched the development of human genetics as well as its assimilation into the broader context of science, medicine, and health.

Introduction: David Valle, MD, Johns Hopkins University

Recipient:

James R. Lupski
James Lupski, MD, PhD, Baylor College of Medicine

Dr. Lupski has substantially defined the field of genomic medicine and his lab’s work has helped to foster the precision medicine initiative. Dr. Lupski showed that CMT1A copy number variation (CNV) and gene dosage are causes of CMT-related peripheral nerve dysfunction. In 2014, he and his colleagues found that the presence of three copies of CMT1A on one chromosome 17, a phenomenon known as triplication, causes a more severe form of CMT. Throughout, his research has focused on understanding mutational mechanisms and linking specific mutations and genes to human disease.

 


Tuesday, October 16

5:15 PM–5:30 PM

3. ASHG Curt Stern Award Presentation and Lecture: Genetic Basis for Heart Attack

Hall C, Ground Level, San Diego Convention Center

The ASHG Curt Stern Award recognizes genetics and genomics researchers who have made significant scientific contributions during the past decade.

Introduction: Goncalo Abecasis, PhD, Univ Michigan, Ann Arbor

Recipient:
Sekar Kathiresan
Sekar Kathiresan, MD, Massachusetts General Hospital/Harvard Medical School, Broad Institute of MIT and Harvard, Boston

Dr. Kathiresan has pursued a systematic approach to understand the genetics underlying risk of heart attack, to discover its root causes, inform new therapeutic approaches, and identify at-risk individuals. His research program has highlighted triglyceride-rich lipoproteins and the ANGPTL3 gene as a therapeutic target, uncovered new non-lipid mechanisms contributing to heart attack, and developed a genome interpretation framework that delineates monogenic, somatic, and polygenic drivers of risk for heart attack.

 


Tuesday, October 16

5:30 PM–6:50 PM

4. Featured Plenary Abstract Session I

Hall C, Ground Level, San Diego Convention Center

Moderators: Heather C. Mefford, ASHG 2018 Program Chair
  Kiran Musunuru, ASHG 2018 Program Committee

 

Featured Plenary Abstract Sessions include a diverse set of presentations selected from the top-rated abstracts across all topics.

 

1/5:30 From GWAS to function: Comprehensive integrated genomic perturbation to reveal molecular mechanisms of trait associations. M.A. Cole, A. Mousas, Y. Wu, J. Zeng, Q. Yao, D. Vinjamur, R. Kurita, Y. Nakamura, L. Pinello, G. Lettre, D.E. Bauer.

2/5:50 Incidence of uniparental disomy in 2 million individuals from the 23andMe database. P. Nakka, K. McManus, A. O'Donnell-Luria, U. Francke, J. Mountain, S. Ramachandran, F. Sathirapongsasuti, 23andMe Research Team.

3/6:10 Discovery and characterization of 102 genes associated with autism from exome sequencing of 37,269 individuals. J.A. Kosmicki, F.K. Satterstrom, J. Wang, R.L. Collins, S. de Rubeis, M. Breen, S. Gerges, M. Peng, X. Xu, C. Stevens, JJ. Grove, A.D. Børglum, J.D. Buxbaum, D.J. Cutler, B. Devlin, K. Roeder, S.J. Sanders, M.E. Talkowski, M.J. Daly, Autism Sequencing Consortium.

4/6:30 Inhibition of oxytocin signaling prevents pregnancy-associated aortic dissection in a novel mouse model of vascular Ehlers-Danlos Syndrome. C.J. Bowen, G. Rykiel, J.C. Giadrosic, J. Habashi, M. Helmers, H.C. Dietz.


Tuesday, October 16

7:00 PM–8:00 PM

5. Poster Talks: Two Concurrent Sessions

Rooms 6C and 6D, Upper Level, San Diego Convention Center

Moderators: Beryl B. Cummings, ASHG 2018 Program Committee
  Olivia G. Corradin, ASHG 2018 Program Committee

 

Through rapid-fire presentations, these two concurrent sessions provide a sneak peek at some of the top-scoring posters across a variety of topics. Arrive early to network with fellow attendees over light refreshments. Conversations with the presenters will continue at the Poster Sessions throughout the meeting. The event is open to all scientific registrants.

Session I (Room 6C): Clinical and Mendelian Genetics
Session II (Room 6D): Complex Traits and Statistical Genetics
To view which posters will be presented in each session, click here.

 

428T    A de novo CNV deletion of the FOXF1 enhancer in 16q24.1 unmasks a rare noncoding SNP that likely prevented a lethal ACDMPV phenotype. P. Szafranski, V. Poisson, D. Bérubé, L. Oligny, J.L. Michaud, P. Stankiewicz.

432F    Global protein-protein and protein-DNA interactions of DNA topoisomerases. L. Uuskula-Reimand, P. Samavarchi-Tehrani, H. Hou, K. Abe, R. Ostadsharif Memar, S. Akhtar Alvi, J. Reimand, A.C. Gingras, M.D. Wilson.

521T    Full-gene sequencing based expanded carrier screening of over 150 disorders. C. Gijavanekar, B. Yuan, J. Scull, Z. Chen, L. Meng, S. Wen, R. Xiao, J. Zhang, E. Schmitt, S. Peacock, J. Dong, H. Cheng, D. Muzny, R. Gibbs, A. Beaudet, F. Xia, C. Eng.

533T    When is a disease too rare? A statistical framework for estimating clinical sensitivity for expanded carrier screening panels. R. Ben-Shachar, A. Svenson, D. Muzzey.

593T    Long-term impact of presymptomatic genetic testing for HD: Family narratives. J.M. Bollinger, K.M. Stuttgen, A. McCague, R.L. Dvoskin, B. Shpritz, J. Brandt, D.J.H. Mathews.

594F    The burden of biased variant datasets: Examining enrollment and candidate genes for non-European rare disease probands in the Duke Task Force for Neonatal Genetics. E.F. Bullis, E.M. Ghanaim, A. Sadeghpour, E.E. Davis, S.H. Katsanis.

659F    Assessing the prevalence and clinical implications of secondary findings for hereditary cancer predisposition among patients with chronic kidney disease. E. Groopman, M. Marasa, S. Sanna-Cherchi, K. Kiryluk, D. Goldstein, A. Gharavi.

742T    Increased penetrance of acute lymphoblastic leukemia susceptibility loci in children with Down syndrome. A.J. de Smith, A.L. Brown, V.U. Gant, M.E. Scheurer, K.M. Walsh, N.J. Winick, N.A. Heerema, A.J. Carroll, M.J. Borowitz, B.L. Wood, W.L. Carroll, E.A. Raetz, E. Feingold, W. Yang, M. Devidas, D. Sinnett, C.G. Mullighan, S.P. Hunger, C.H. Pui, M. Loh, M.E. Zwick, C. Metayer, X. Ma, B.A. Mueller, S.L. Sherman, J.L. Wiemels, J.J. Yang, M.V. Relling, P.J. Lupo, K.R. Rabin.

1122W    Inherited peripheral neuropathies: Analysis of PDXK gene identifies a new treatable disorder. V. Chelban, J. Vandrovcova, M. Wilson, S. Efthymiou, E. Zamba-Papanicolaou, N. Wood, P. Mills, P. Clayton, H. Houlden, SYNAPSE Study Group.

1260W    Missense variants in PLS3 in patients with X-linked congenital diaphragmatic hernia. F. Petit, B.R. Pober, R.D. Clark, P. Giampietro, H.H. Ropers, H. Hu, A-S. Jourdain, F. Frenois, M-A. Delrue, B. Gilbert-Dussardier, L. Devisme, B. Keren, S. Manouvrier-Hanu, P. Bhayani, M. Loscertales, P.K. Donahoe, F.A. High, M. Longoni.

1474T    Deep linear mixed models for structured, high-dimensional trait GWAS. F.P. Casale, A.V. Dalca, N. Fusi, J. Listgarten.

1519T    Meta-analysis of vaginal microbiome data provides new insights into preterm birth. I. Kosti, S. Lyalina, KS. Pollard, AJ. Butte, M. Sirota.

1714T    Fine-mapping autoimmune disease variants in cytokine induced cell states. B. Soskic, E.C. Gamez, D. Plowman, N. Nakic, D. Tough, W. Rowan, C. Larminie, T. Carlson, P.G. Bronson, K. Estrada, G. Trynka.

1774T    Returning unanticipated genomic results in a hospital-based research biobank. R.C. Green, C.L. Blout, M.S. Lebo, J.B. Krier, J. Smoller, E.W. Karlson, L. Mahanta, K. O'Brien, K.D. Christensen, N. Boutin, S.T. Weiss.

2012F    A limited set of transcriptional programs define major histological types and provide the molecular basis for a cellular taxonomy of the human body. A. Breschi, M. Muñoz-Aguirre, D. Garrido-Martín, C. Davis, V. Wucher, S. Djebali, J. Gillis, D. Pervouchine, A. Vlasova, A. Dobin, C. Zaleski, J. Drenkow, C. Dnyko, A. Scavelli, F. Reverter-Comas, T. Gingeras, R. Guigó.

2022W    Somatic activating mutations in MAP2K1 cause melorheostosis. J.C. Marini, H. Kang, S. Jha, Z. Deng, N. Fratzl-Zelman, W.A. Cabral, A. Ivovic, F. Meylan, E.P. Hanson, E. Lange, J. Katz, P. Roschger, K. Klaushofer, E.W. Cowen, R.M. Siegel, T. Bhattacharyya.

2061W    Using Xenopus laevis as a model for studying genes associated with intellectual disabilities. M. Lasser, L. Pizzo, J. Tiber, C. Monahan, S. Kim, S. Lee, S. Girirajan, L.A. Lowery.

2432F    Towards an understanding of the genetic architecture of the human cortex: Examining the effects of common variants on cortical thickness and surface area. S.E. Medland, The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium.

2769W    Mapping African ancestry among African Americans. C.C. Jones, P.S. Ramos, S.J. Chanock, S.A. Tishkoff, S.M. Williams, M.C. Aldrich, African American Lung Cancer Consortium.

2783F    Interpreting variants of uncertain significance using common variation in non-human primates. H. Gao, L. Sundaram, S. Reddy, J. McRae, S. Batzoglou, K. Farh.

2959T    The complex genetic architecture of mitochondrial disease: Exploration of 1500 cases by whole exome sequencing. S.L. Stenton, B. Alhaddad, C. Chang, T. Haack, S. Wortmann, J. Mayr, B. Büchner, P. Freisinger, C. Makowski, D. Rokicki, R. Taylor, F. Fang, K. Murayama, Y. Okasaki, D. Ghezzi, C. Lamperti, A. Rötig, T. Strom, T. Klopstock, T. Meitinger, H. Prokisch.

3010T    Mate pair sequencing: Ushering cytogenetics into the era of personalized medicine. N. Hoppman, B. Pitel, S. Smoley, S. Johnson, J. Smadbeck, M. Webley, S. Koon, L. Baughn, G. Vasmatzis, E. Thorland, H. Kearney.

3145T    Overview of the NHLBI Trans-Omics for Precision Medicine (TOPMed) program: Whole-genome sequencing of >100,000 deeply phenotyped individuals. C. Laurie, T. Blackwell, G. Abecasis, K. Rice, J. Wilson, D. Nickerson, S. Gabriel, R. Gibbs, S. Dutcher, S. Germer, D. Arnett, A. Ashley-Koch, K. Barnes, E. Boerwinkle, S. Rich, E. Silverman, R. Beer, J. Mikulla, P. Srinivas, W. Gan, G. Papanicolaou, C. Jaquish, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium.

3163T    Genome-wide association study of the QRS complex. K. Norland, G. Sveinbjornsson, R.B. Thorolfsdottir, O.B. Davidsson, V. Tragante, D.O. Arnar, R. Danielsen, S.S. Stephensen, G. Oskarsson, G. Thorgeirsson, J.T. Sverrisson, E.L. Sigurdsson, K. Andersen, A. Helgadottir, S. Gretarsdottir, P. Sulem, U. Thorsteinsdottir, H. Holm, D.F. Gudbjartsson, K. Stefansson.

3340T    Genome-wide association studies of brain structure and function in the ~20,000 UK Biobank participants. K.J. Sharp, L.T. Elliott, F. Alfaro-Almagro, S. Shi, K. Miller, G. Douaud, J. Marchini, S. Smith.

3445T    Hepatic gene expression and DNA methylation associates with African ancestry: Uncovering the role of the genome in disease disparities in African Americans. C.S. Park, Y. Xu, Y. Zhong, C. Alarcon, T. De, M.A. Perera.


Wednesday, October 17

9:00 AM–10:00 AM

Concurrent Platform Session A

6. Variant Insights from Large Population Datasets

Ballroom 20A, Upper Level, San Diego Convention Center

Moderators: Sean Tavtigian, Huntsman Cancer Inst, Salt Lake City
  Jessica Chong, Univ Washington, Seattle

 

NOTE: Overflow seating for this session is available in Room 32AB.

 

5/9:00 Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance in human genes. K.J. Karczewski, L.C. Francioli, G. Tiao, R.L. Collins, B.B. Cummings, J.A. Kosmicki, Q. Wang, A. Ganna, L.D. Gauthier, E. Banks, K.M. Laricchia, J. Alfoldi, T. Poterba, A. Wang, C. Seed, M.E. Talkowski, B.M. Neale, M.J. Daly, D.G. MacArthur, The Genome Aggregation Database Consortium.

6/9:15 A comprehensive study of essential genes, Mendelian disease genes, and loss-of-function-tolerant genes. P.D. Evans, E.R. Gamazon.

7/9:30 Using Exomiser for rare disease variant interpretation at scale in the 100,000 Genomes Project. D. Smedley, J.O. Jacobsen, A.R. Martin, C. Johnson, C. Boustred, K. Smith, E. Thomas, H. Brittain, J. McMurry, M. Haendel, C. Mungall, P.N. Robinson, M. Cauflield, A. Rendon.

8/9:45 Assessment of penetrance of 10 Mendelian disease states in 46,980 exomes. J.K. Goodrich, J.C. Wood, S. Baxter, A. O'Donnell-Luria, B. Weisburd, Z. Zappala, J. Mercader, J. Flannick, J.C. Florez, D. MacArthur, M.S. Udler, AMP-T2D consortium.


Wednesday, October 17

9:00 AM–10:00 AM

Concurrent Platform Session A

7. GWAS in Combined Cancer Phenotypes

Ballroom 20BC, Upper Level, San Diego Convention Center

Moderators: Michael Walsh, Memorial Sloan Kettering Cancer Ctr, New York
  Katrina Goddard, Kaiser Permanente Ctr Hlth Res, Portland

 

9/9:00 Joint genome-wide association study of endometrial cancer and ovarian cancer identifies novel genetic risk regions at 7p22.2 and 14q23.3. T.A. O'Mara, D.M. Glubb, D.J. Thompson, A.B. Spurdle, OCAC, ECAC.

10/9:15 Combining genetic and exposure data significantly improve risk prediction for skin cancer. P. Fontanillas, B. Alipanahi, M. Johnson, C. Wilson, A. 23andMe Research Team, S. Pitts, R. Gentleman, A. Auton.

11/9:30 Pan-cancer analysis detects novel genetic risk variants and shared genetic basis in the UK biobank cohort. S.R. Rashkin, R.E. Graff, L. Kachuri, T.J. Meyers, N.C. Emami, K.K. Thai, S.E. Alexeeff, D.A. Corley, L.H. Kushi, S.K. Van Den Eeden, E. Jorgenson, L.A. Habel, L.C. Sakoda, T.J. Hoffmann, E. Ziv, J.S. Witte.

12/9:45 Large scale genome-wide association meta-analysis of melanoma identifies 69 independent variants in 56 loci including immune related genes. M.H. Law, J. Shi, D.T. Bishop, K.M. Brown, A.J. Stratigos, M.C. Fargnoli, P. Ghiorzo, K. Peris, A.E. Cust, J. Han, D.C. Whiteman, D. Schadendorf, G.J. Mann, G.L. Radford-Smith, N.G. Martin, C. Hayward, N.K. Hayward, G.W. Montgomery, S.V. Ward, P.D.P. Pharoah, C.I. Amos, M. Zawistowski, S. Puig, D.L. Duffy, F. Demenais, E. Nagore, S. MacGregor, M.M. Iles, M.T. Landi, UK Biobank, 23andMe Research Team.


Wednesday, October 17

9:00 AM–10:00 AM

Concurrent Platform Session A

8. Genome-wide Epigenomics and Non-coding Variants

Ballroom 20D, Upper Level, San Diego Convention Center

Moderators: Ryan Tewhey, Jackson Lab, Bar Harbor
  Christina Castellani, Johns Hopkins Univ Sch Med, Baltimore

 

13/9:00 High-resolution epigenomic atlas of human embryonic craniofacial development. J. Cotney, A. Wilderman, J. VanOudenhove, J.P. Noonan.

14/9:15 Rheumatoid arthritis heritability is concentrated in regulatory elements with CD4+ T cell-state-specific transcription factor binding chromatin signatures. T. Amariuta, Y. Luo, E. Davenport, S. Gazal, B. van de Geijn, H.J. Westra, N. Teslovich, A. Price, S. Raychaudhuri.

15/9:30 Uniformly collected and processed functional genomics assays provide a way to interpret non-coding variants in terms of tissue of action. F.C.P. Navarro, G. Gursoy, J. Rozowsky, A. Dobin, T. Galeev, X. Kong, A. Vlasova, R. Guigo, M. Schatz, T. Gingeras, M. Gerstein.

16/9:45 Development of a comprehensive, curated database of open chromatin regions of 192 cell types. P. Shooshtari, C. Cotsapas.


Wednesday, October 17

9:00 AM–10:00 AM

Concurrent Platform Session A

9. Clonal Mosaicism in Cancer, Alzheimer's Disease, and Healthy Tissue

Room 6A, Upper Level, San Diego Convention Center

Moderators: Adam Locke, Washington Univ, St. Louis
  David Buchner, Case Western Reserve Univ, Cleveland

 

17/9:00 Mosaic chromosomal alterations increase proliferative loads from rare coding variants and common polygenic risk. P. Loh, G. Genovese, S.A. McCarroll.

18/9:15 Clonal mosaicism in normal TCGA tissues. Y.A. Jakubek, J. Fowler, F.A. San Lucas, H. Kadara, P. Scheet.

19/9:30 Identification, characterization, and modeling of genomic mosaicism among multiple tissues of healthy individuals. Y. Huang, Y. Ye, Y. Dou, X. Yang, S. Wang, X. Zheng, L. Wei.

20/9:45 Leveraging single-cell RNA-seq to infer cell type-specific somatic mutations and mosaicism in Alzheimer’s disease. C. Boix, M. Kousi, H. Mathys, L. Tsai, M. Kellis.


Wednesday, October 17

9:00 AM–10:00 AM

Concurrent Platform Session A

10. Genetics of Behavioral Traits and Diseases

Room 6B, Upper Level, San Diego Convention Center

Moderators: Christina Markunas, RTI International, Washington, D.C.
  Eric Jorgenson, Kaiser Permanente, Oakland

 

21/9:00 Genetic studies of accelerometer-based sleep measures in 85,670 individuals yield new insights into the biology of human sleep behaviour. S.E. Jones, V.T. van Hees, D.R. Mazzotti, P. Marques-Vidal, S. Sabia, A. van der Spek, H.S. Dashti, J. Engmann, D. Kocevska, J. Tyrrell, R.N. Beaumont, M. Hillsdon, K.S. Ruth, M.A. Tuke, H. Yaghootkar, J.W. Harrison, R.M. Freathy, A. Murray, A.I. Luik, N. Amin, J.M. Lane, R. Saxena, M.K. Rutter, H. Tiemeier, Z. Kutalik, M. Kumari, T.M. Frayling, M.N. Weedon, P. Gehrman, A.R. Wood.

22/9:15 Moderate alcohol consumption is causally related to higher risk of coronary heart disease and stroke: A Mendelian randomization analysis in the UK Biobank. J. Lankester, D. Zanetti, T.L. Assimes, E. Ingelsson.

23/9:30 GWAS for anorexia nervosa identifies eight loci and suggests it is both a psychiatric and metabolic disorder. N. Martin, C. Bulik, Anorexia Nervosa Genetics Initiative (ANGI).

24/9:45 Genome-wide association study of tobacco smoking among European Americans in Million Veteran Program (MVP). B. Li, A.C. Justice, K.A. McGinnis, N. Sun, R.V. Smith, C. Dao, J.P. Tate, W.C. Becker, J. Concato, J. Gelernter, H.R. Kranzler, H. Zhao, K. Xu, VA Million Veteran Program.


Wednesday, October 17

9:00 AM–10:00 AM

Concurrent Platform Session A

11. New Frontiers in Computational Genomics

Room 6C, Upper Level, San Diego Convention Center

Moderators: Fritz Sedlazeck, Baylor Col Med, Houston
  Meeshanthini Dogan, Univ Iowa, Iowa City

 

This session is not eligible for continuing education credit.

NOTE: Overflow seating for this session is available in Room 2.

 

25/9:00 Discovering genotype specific effects of inducing pluripotency in a mix pool of many donor cells without the use of exogenous DNA barcodes or single-cell sequencing. Y. Chan, E.T. Lim, G.M. Church.

26/9:15 Targeted full-length transcriptome sequencing to confirm gene models identifies novel isoforms. E. Tseng, G. Sheynkman, D. Hill, M. Vidal.

27/9:30 Characterization of de novo mutations in an unascertained large clinical cohort. A. Blumenfeld, J. Staples, O. Gottesman, J.D. Overton, J.G. Reid, D. Carey, M. Murray, C. Gonzaga-Jauregui, Geisinger-Regeneron DiscovEHR.

28/9:45 Private information leakage from raw functional genomics data: Theoretical quantifications & practical privacy-aware file formats. G. Gursoy, A. Harmanci, M. Green, F. Navarro, M. Gerstein.


Wednesday, October 17

9:00 AM–10:00 AM

Concurrent Platform Session A

12. Bone and Muscle: Identifying Causal Genes

Room 6D, Upper Level, San Diego Convention Center

Moderator: Andrew S. McCallion, Johns Hopkins Univ Sch Med, Baltimore

 

This session is not eligible for continuing education credit.

 

29/9:00 An atlas of human and murine genetic influences on osteoporosis. J.A. Morris, J.P. Kemp, S.E. Youlten, L. Laurent, J.G. Logan, R. Chai, N.A. Vulpescu, V. Forgetta, A. Kleinman, S. Mohanty, C.M. Sergio, J. Quinn, L. Nguyen-Yamamoto, A.L. Luco, J. Vijay, C.L. Gregson, N.C. Harvey, E. Grundberg, D. Goltzman, D.J. Adams, C.J. Lelliott, D.A. Hinds, C.L. Ackert-Bicknell, Y-H. Hsu, M.T. Maurano, P.I. Croucher, G.R. Williams, J.H.D. Bassett, D.M. Evans, J.B. Richards, GEFOS Consortium.

30/9:15 Qsox1 is a novel genetic determinant of bone size in mice. B.M. Al-Barghouthi, G.M. Calabrese, L.D. Mesner, K. Nguyen, M.L. Bouxsein, D. Brooks, M.C. Horowitz, C.J. Rosen, S.M. Tommasini, P. Simecek, G.A. Churchill, C.L. Ackert-Bicknell, D. Pomp, C.R. Farber.

31/9:30 COPB2 loss of function leads to disrupted collagen trafficking and juvenile osteoporosis. R. Marom, L.C. Burrage, M. Jain, I. Grafe, D.A. Scott, M. Shinawi, J.A. Rosenfeld, J.D. Heaney, D. Lanza, Y.C. Lee, I.W. Song, J.M. Sliepka, D. Batkovskyte, Z. Jin, B. Dawson, S. Chen, Y. Chen, M.M. Jiang, V.R. Sutton, C. Kuzawa, R. Venditti, M.A. Weis, A. Clément, B. Tremp, B. Blanco-Sánchez, M. Westerfield, D. Eyre, C.G. Ambrose, M.A. De Matteis, B.H. Lee, Members of the Undiagnosed Diseases Network.

32/9:45 Variant to gene mapping strategies to maximize gene identification from a GWAS of grip strength in UK Biobank. D.M. Waterworth, D. Rajpal, K. Guo, J. Freudenberg, K.B. Sieber, A. Pandey, I. Tachmazidou, R.A. Scott.


Wednesday, October 17

9:00 AM–10:00 AM

Concurrent Platform Session A

13. Precision Medicine Initiatives: Outcomes and Lessons Learned

Room 6E, Upper Level, San Diego Convention Center

Moderators: Cheryl Shuman, Univ Toronto, Canada
  Barbara Biesecker, Research Triangle Inst, Intl, Washington, D.C.

 

NOTE: Overflow seating for this session is available in Rooms 7A, 7B, and 5AB.

 

33/9:00 Proactive genetic testing in a primary care setting reveals unexpected results. J. Gu, A. Hazell, M. Zarb, J. Furnival, L. Velsher.

34/9:15 The Alabama Genomic Health Initiative. B.R. Korf, G.S. Barsh, K.M. Bowling, A. Cannon, J.J. Cimino, G.M. Cooper, W.A. Curry, K. East, J. Edberg, M. Fouad, A.C. Hurst, M. Might, S.J. Knight, T. May, I.P. Moss, M. Nakano, J.H. Schach, B.M. Shaw, S.O. Sodeke.

35/9:30 The Integrating Pharmacogenetics in Clinical Care (I-PICC) study: Baseline characteristics of participants in a point-of-care randomized trial. S. Advani, C.A. Brunette, S.J. Miller, N. Majahalme, L. MacMullen, C. Hau, A.J. Zimolzak, J.L. Vassy.

36/9:45 Prevalence of pathogenic variants in actionable genes for neurological disorders in the Geisinger MyCode Initiative. V. Abedi, R. Zand, T.N. Person, A. Sadeghi, S.J. Thakur, Y. Zhang, M.T.M. Lee, N.E. Andary, C. Griessenauer, A.M. Michael, M.C. Sandulescu, N. Holland, A. Sarkar, C.M. Schirmer, N. Martin, M.S. Williams, D.J. Carey.


Wednesday, October 17

9:00 AM–10:00 AM

Concurrent Platform Session A

14. Environmental Exposures in Human Traits

Room 6F, Upper Level, San Diego Convention Center

Moderators: Kerrin Small, King's Col London, UK
  Heather Wheeler, Loyola Univ Chicago

 

37/9:00 Genetic and environmental effects disrupt molecular co-regulation. A.J. Lea, M. Subramaniam, A. Ko, T. Lehtimäki, E. Raitoharju, M. Kähönen, I. Seppälä, N. Mononen, O. Raitakari, M. Ala-Korpela, P. Pajukanta, N.A. Zaitlen, J.F. Ayroles.

38/9:15 Exposome-wide association study (EWAS) identifies link between pregnancy anxiety and various autism spectrum traits. A. Verma, A. Lucas, I. Hertz-Picciotto, Y. Ludena-Rodriguez, RJ. Schmidt, MD. Ritchie.

39/9:30 Do gene-environment interactions matter in multifactorial diseases? V. Laville, Y.J. Sung, T.W. Winkler, M. Province, K. Rice, S. Kardia, J. Gauderman, D.C. Rao, H. Aschard, CHARGE Gene-Lifestyle Interactions Working Group.

40/9:45 Dynamic human environmental exposome revealed by longitudinal personal monitoring. C. Jiang, X. Wang, X. Li, J. Inlora, T. Wang, Q. Liu, M. Snyder.


Wednesday, October 17

10:30 AM–12:30 PM

Concurrent Invited Session I

15. Achieving Genomics Literacy for the Masses: Providing Meaningful Education for Multiple Audiences

Room 6C, Upper Level, San Diego Convention Center

Moderators: Adam M. Hott, HudsonAlpha Inst for Biotech, Huntsville
  Rivka Glaser, Stevenson Univ, Owings Mills

 

NOTE: Overflow seating for this session is available in Room 2.

Twitter: “@GeneticsSociety How do we communicate in the classroom, café and clinic the importance of genomics? We must to battle funding decline and spot #fakenews #genomicliteracy.” The utility of genomic research from food production to infection diagnostics and the integration of genomics in medical practice is quickly becoming a standard conversation from the lunch table to Twittersphere to the general practitioner’s office visit. It is now more important than ever to ensure genomics literacy across the spectrum of age ranges and career specialties. Achieving that for groups as diverse as K‑12 students, the general public, or healthcare providers is nuanced and can be difficult to navigate. This session explores ongoing efforts to increase genomics literacy for K‑12, undergraduate, general public and pre‑healthcare/healthcare provider audiences from NHGRI’s Genomics Literacy, Education, and Engagement (GLEE) to the development of the CSER Consortium’s Guide to Interpreting Genomic Reports: A Genomics Toolkit for non‑genetics healthcare practitioners.

 

10:30 AM   Genomic literacy for K-16 audiences: Efforts to develop a national campaign to enhance genomic literacy. E. Tuck. NIH/NHGRI, Bethesda.

11:00 AM   The Genomics Education Partnership: Expanding opportunities for undergraduate research in genomics. S. C. Elgin. Washington Univ St Louis.

11:30 AM   Supporting the practice of genomic medicine on the front lines. K. M. East. HudsonAlpha Inst Biotech, Huntsville.

12:00 PM   Doing science is not enough: The importance of communicating your research in any way you can. C. Gunter. Emory Univ Sch Med, Atlanta.


Wednesday, October 17

10:30 AM–12:30 PM

Concurrent Invited Session I

16. Chromatin Dysregulation in Neurodevelopmental Disorders

Room 6B, Upper Level, San Diego Convention Center

Moderators: Shigeki Iwase, Univ Michigan Med Sch, Ann Arbor
  Anne E. West, Duke Univ Sch Med, Durham

 

Neurodevelopmental disorders, including autism spectrum disorders, intellectual disability, and schizophrenia, are prevailing conditions associated with impaired cognitive and adaptive behavior. Many chromatin regulators have been genetically associated with neurodevelopmental disorders, and we have begun to understand the molecular and cellular basis of these disorders. In this session, leading experts will discuss how chromatin contributes to normal brain development and how altering the functions of histone modifiers and chromatin remodelers in disease impairs neurodevelopment. The first speaker, Shigeki Iwase, focuses on regulators of histone H3K4 methylation and discusses how this chromatin modification contributes to normal and pathological brain development. Next, Elena Battaglioli highlights the unique chromatin regulation within neurons via neuron-specific alternative splicing of a histone demethylase. The third speaker, Anne West, discusses how repressive histone H3K27 methylation controls the temporal maturation of postmitotic neurons. Finally, David Picketts explains the roles of ATP-dependent chromatin remodeling enzymes in brain development. While the session aims to shed new light on fundamental chromatin regulations leading to normal brain development and function, it will also provide clinical insights into how we diagnose, discover pathophysiological mechanisms, and eventually ameliorate neurodevelopmental disorders.

 

10:30 AM   Balancing and reading H3K4 methylation in neurodevelopmental disorders. S. Iwase. Univ Michigan Med Sch, Ann Arbor.

11:00 AM   Neuron-specific LSD1 controls plasticity-related transcription and provides a clue to deciphering intellectual disability. E. Battaglioli. Univ Milan, Italy.

11:30 AM   Chromatin regulation of neuronal maturation. A. E. West. Duke Univ Sch Med, Durham.

12:00 PM   Unraveling the mechanisms of aberrant chromatin remodeling associated with intellectual disability. D. Picketts. Univ Ottawa, Canada.


Wednesday, October 17

10:30 AM–12:30 PM

Concurrent Invited Session I

17. Clinical Spotlight: Realizing the Promise of Common Genomic Variation in Rare and Common Disease: Clinical Implementation of Polygenic Risk Scores

Ballroom 20BC, Upper Level, San Diego Convention Center

Moderators: Amanda E. Toland, Ohio State Univ, Columbus
  Alison H. Trainer, Peter MacCallum Cancer Inst & Univ Melbourne, Parkville, Australia

 

Whilst the contribution of common genomic variation to both rare and common disorders has informed both human physiology and disease etiology, its translation into the clinical setting is only now emerging. Individually each variant is of poor predictive or diagnostic value due to its low effect size, but evidence is emerging that an individualized combinatorial polygenic risk score (PRS) may have utility in both population-based and clinic-based medicine. Clinical trials are currently investigating the use of PRS-based assessments to aid in individual diagnosis or as a means of stratifying, and thereby appropriately targeting, disease risk at a population level in order to increase diagnosis rate and cost-efficiency. In this session, we will highlight the clinical uses of PRS using results from current studies from a variety of medical specialties including cancer, cardiovascular disease, Alzheimer’s disease and autism, and spanning different aspects of care from disease prevention to diagnosis and treatment. The session will also demonstrate the interplay between PRS and additional monogenic variants and environmental factors in determining clinical phenotypes.

 

10:30 AM   Use of the polygenic risk score as part of breast cancer risk assessment in the WISDOM Risk Thresholds Trial. E. Ziv. UCSF.

11:00 AM   Polygenic risk score analysis in the pre-symptomatic prediction and diagnosis of Alzheimer’s disease. V. Escott-Price. Cardiff Univ, United Kingdom.

11:30 AM   Polygenic risk scores as a determinant of autism spectrum disorder heterogeneity. E. Robinson. Harvard Sch Publ Hlth & Broad Inst, Cambridge.

12:00 PM   Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. S. Kathiresan. Massachusetts Gen Hosp, Boston.


Wednesday, October 17

10:30 AM–12:30 PM

Concurrent Invited Session I

18. Large Scale Functional Annotation of Variants of Uncertain Significance

Ballroom 20D, Upper Level, San Diego Convention Center

Moderators: Stan Letovsky, LabCorp, Westborough
  Alice Berger, Fred Hutchinson Cancer Res Ctr, Seattle

 

Genomic tools and analysis methods are enabling investigation of the functional effects of genetic variants at high-throughput. New methods of controlled mutagenesis, such as the CRISPR/Cas9 system, allow systematic exploration of the space of possible mutations. Functional assays based on flow cytometry, minigene reporters, or differential survival, often using next-generation sequencing as a readout, demonstrate a growing toolkit of methods for assessing functional impacts. Machine learning approaches are being applied to these datasets to estimate the probability of pathogenicity. Taken together these tools provide a powerful and scalable approach to understanding functional impacts of genetic variants where clinical or population data are lacking. This session will feature presentations from leaders in this exciting new field, using as a primary example the BRCA genes and their impact on cancer risk.

 

10:30 AM   Gene editing, flow sorting and sequencing to address the challenge of annotating variants of uncertain significance. H. Ostrer. Albert Einstein Col Med, New York.

11:00 AM   Accurate functional classification of thousands of BRCA1 variants with saturation genome editing. L. M. Starita. Univ Washington, Seattle.

11:30 AM   Clinical annotation of BRCA1 VUS through functional assays. N. T. Woods. Univ Nebraska Med Ctr, Omaha.

12:00 PM   High-throughput splicing screen of genetic variants of unknown significance. W. Fairbrother. Brown Univ, Providence.


Wednesday, October 17

10:30 AM–12:30 PM

Concurrent Invited Session I

19. New Developments in Mendelian Randomization

Room 6A, Upper Level, San Diego Convention Center

Moderators: David M. Evans, Univ Queensland, Brisbane, Australia
  Brent Richards, McGill Univ, Montreal, Canada

 

Mendelian Randomization (MR) is a statistical method that uses genetic variants as instrumental variables to inform causal relationships. Initial applications of MR mostly focused on estimating the causal effect of environmental exposures on medically relevant outcomes. In recent years, MR has found considerable utility across a wide range of domains including in the development of pharmaceutical agents (i.e., drug target validation, drug repurposing, and side effect identification) and in the interpretation of high-dimensional -omics studies. In this session, we discuss some of the latest breakthroughs in the development and application of the MR methodology. This includes using MR to inform drug development (including using high dimensional -omics data), performing MR studies of disease progression (which is potentially more informative in terms of disease treatment than MR studies of disease risk), developing new strategies to deal with the pervasive issue of pleiotropy in MR analyses, and using MR to investigate the causal influence of maternal exposures on offspring outcomes.

This session is not eligible for continuing education credit.

 

10:30 AM   Mendelian randomization and disease progression: Challenges and opportunities. G. Davey Smith. Univ Bristol, United Kingdom.

11:00 AM   Mendelian randomization in drug discovery and development. R. Scott. Glaxo-Smith Kline, Stevenage, United Kingdom.

11:30 AM   Evaluation of horizontal pleiotropy among causal relationships inferred from MR between complex traits and diseases. R. Do. Icahn Sch Med Mount Sinai, New York.

12:00 PM   Using Mendelian randomization to disentangle maternal and fetal contributions to low birth weight and future risk of cardio-metabolic disease. N. Warrington. Univ Queensland, Brisbane, Australia.


Wednesday, October 17

10:30 AM–12:30 PM

Concurrent Invited Session I

20. Silent Genomes: Indigenous-led Initiatives on Addressing Equity in Genomics Health Care and Research

Room 6E, Upper Level, San Diego Convention Center

Moderators: Nanibaa' A. Garrison, Seattle Children’s Res Inst
  Keolu Fox, UCSD

 

Indigenous populations worldwide face unique health challenges, inequities, and barriers to healthcare. As such, they typically have poorer health outcomes than do non-Indigenous groups. While genetics/genomics research has greatly advanced health outcomes in mainstream populations, there is danger of increasing health inequities including the ‘genomic divide’. The ‘genomic divide’ is a much written-about, complicated reality that is based in unequal access to genomic technologies and social-economic determinants, and also considers the lack of relevant background genetic variation data, potentially preventing accurate diagnosis and limiting effectiveness of genetic/genomic research. Indigenous people may be hesitant to participate in genetic/genomic research and clinical testing when it is available. Historical and current reasons that might prevent participation include unconsented secondary use of biological samples (including research that traces ancestry), funding agency requirements for data sharing, conflicting researcher/community priorities, and general concerns of exploitation of Indigenous communities for the benefit of mainstream science and economics. Throughout the United States, Canada, Australia and New Zealand, Indigenous scholars are leading initiatives to improve access to genetic/genomic research and healthcare based in their unique cultural context and within governance models acceptable to their populations. We welcome an engaged audience, including through our Twitter hashtag #IndiGenomics. Our all-Indigenous international panel will be co-moderated by a bioethicist (@NanibaaGarrison) and genomic scientist (@KeoluFox) and will consist of a highly interdisciplinary group of experts, including a surgeon, internist, epidemiologist and translational researcher, who will present the initiatives they are involved in, within their respective regions, to narrow the genomic divide.

 

10:30 AM   Un-silencing genomes: Introduction to the panel. N. A. Garrison. Seattle Children’s Res Inst.

10:40 AM   Misuse & abuse: When good intentions result in harm. M. Taualii. Univ Hawaii, Manoa, Honolulu.

10:50 AM   Addressing inequity in genomic diagnosis and research: Development of governance and culturally relevant policies. N. Caron. Univ British Columbia, Prince George, Canada.

11:00 AM   Australian Aboriginal culture, genomics and biobanking. N. Brown. South Australian Hlth & Med Res Inst, Wollongong, Australia.

11:10 AM   Building an indigenous genomics platform in Aotearoa New Zealand. M. Hudson. Univ Waikato, Hamilton, New Zealand.

11:20 AM   Indigenizing genomics: A synthesis and introduction to panel discussion. K. Fox. UCSD.

11:30 AM   Panel discussion.


Wednesday, October 17

10:30 AM–12:30 PM

Concurrent Invited Session I

21. Technical Approaches and Guidelines for Protecting Privacy of Genetic Data

Room 6D, Upper Level, San Diego Convention Center

Moderator: Armin Pourshafeie, Stanford Univ

 

NOTE: Overflow seating for this session is available in Room 1AB.

In recent years, the available genetic and health related data has grown at an astonishing rate. The availability and sharing of this data has led to exceptional research opportunities for researchers worldwide. At the same time, negligence in sharing the data can put participants in danger of re-identification. In many cases, re-identification can have severe adverse effects on the participants and can lead to lost trust in the scientists and withdrawal of participation in the future. As a result, it is crucial to 1) understand the risks and 2) develop methods that allow for the progress of science through sharing the data without jeopardizing the participants' privacy. In this line, Yaniv Erlich will introduce the problem and discuss the taxonomy of attacks as well as the trade-offs between privacy and utility of the data. Next, Bradley Malin will talk about new game-theoretical insights that help construct platforms that balance privacy, utility of data, and the adversary's desire to breach a participants' privacy. He will further discuss existing, real-world implementation of data sharing schemes employing these insights. Next, Victoria Popic will discuss her new read-mapping algorithm, Balaur. Balaur allows for scalability by delegating a substantial amount of the computations to the public cloud while staying private. Lastly, Bonnie Berger will discuss recent results on performing GWAS studies, at scale, while ensuring that the information about the underlying data is not leaked. The talks are followed by a panel discussion with all the speakers.

This session is not eligible for continuing education credit.

 

10:30 AM   The hitchhiker's guide for genome hacking. Y. Erlich. MyHeritage/Columbia Univ, Or Yehuda, Israel.

10:50 AM   Achieving genomic privacy through sociotechnical controls. B. Malin. Vanderbilt Univ, Nashville.

11:10 AM   A hybrid cloud read aligner based on MinHash and kmer voting that preserves privacy. V. Popic. Illumina, Inc, San Francisco.

11:30 AM   Secure genome crowdsourcing for million-individual association studies. H. Cho. Massachusetts Inst Technol, Cambridge.

11:50 AM   Panel discussion.


Wednesday, October 17

10:30 AM–12:30 PM

Concurrent Invited Session I

22. Uncovering Missing Heritability in Mendelian Diseases: Lessons from Inherited Eye Diseases

Room 6F, Upper Level, San Diego Convention Center

Moderators: Elfride De Baere, Ghent Univ, Ghent, Belgium
  Elena V. Semina, Med Col Wisconsin, Milwaukee

 

NOTE: Overflow seating for this session is available in Room 7B.

Eye diseases are among the most common inherited human disorders. Around one third of the known genetic defects or syndromes involve the eye. Eye research has often blazed a trail for many disciplines to follow, giving a lead in (functional) genomics, transcriptomics, genome editing, stem cell biology, animal models of disease, and the development of novel therapeutic approaches such as gene therapy. Geneticists have identified a large proportion of the genes underlying genetic eye diseases. However, the coding genetic defects identified only account for part of the morbid genome of inherited eye diseases, suggesting new classes of defects such as non-coding defects or frequent hypomorphic alleles in known or undiscovered eye disease genes. These changes are either largely undetected by conventional genomic strategies or are difficult to interpret. This session brings together a diverse group of experts in gene discovery and mechanisms of disease, bioinformatics, model systems and gene editing. They have been committed to identify genes and functionally characterize genetic defects, both coding and non-coding, that are specifically or predominantly expressed in the eye and therefore play an important role in eye function as well as in the pathogenesis of inherited eye disorders. Together, this session will address knowledge gaps in the pathogenesis of genetic eye diseases through cutting-edge approaches related to bioinformatics, (functional) genomics, genome editing and model systems as a paradigm for precision medicine in Mendelian disease.

 

10:30 AM   Using machine learning to predict genes associated with autosomal dominant eye diseases. C. Rivolta. Univ Lausanne, Switzerland and Univ Leicester, UK.

11:00 AM   The non-coding morbid genome of inherited retinal diseases. E. De Baere. Ghent Univ, Belgium.

11:30 AM   CRISPR/Cas9-mediated evaluation of regulatory elements via genomic deletions in zebrafish. E. V. Semina. Med Col Wisconsin, Milwaukee.

12:00 PM   Frequent alleles in the human population account for a significant fraction of inherited retinal disease and lead to a paradigm shift in genetic data interpretation. R. L. Allikmets. Columbia Univ, New York.


Wednesday, October 17

10:30 AM–12:30 PM

Concurrent Invited Session I

23. Understanding Tumor Heterogeneity from Single Cell Sequencing of Genomes, Transcriptomes, and Epigenomes

Ballroom 20A, Upper Level, San Diego Convention Center

Moderators: Xinying Zheng, 10x Genomics, Pleasanton
  Elham Azizi, Mem Sloan Kettering Cancer Ctr, New York

 

It is well established that tumors are marked by heterogeneity. Our understanding of this heterogeneity has largely been limited to studies of DNA variation, with many key insights about minimal residual disease, treatment-resistant clones, and response to immunotherapy emerging as a result. However, the development of higher-throughput single cell technologies and new applications of that technology have broadened our understanding of tumor heterogeneity to include differences in gene expression, epigenomics, and the tumor microenvironment. These new approaches provide an unprecedented look at the complexity of tumor evolution and provide new markers for metastasis, drug response, and disease state. In this session, we will describe how single cell technologies are being used to identify different types of tumor heterogeneity and how this information is changing our understanding of tumor biology, metastatic processes, and treatment. The session will cover 1) the use of single cell DNA and RNA sequencing to understand the progression from in situ to invasive disease in cancer, 2) single cell barcoding to track the growth and composition of genetically-altered human tumor cells in mouse models of metastasis, 3) how epigenomic heterogeneity can be used to identify key regulatory pathway differences associated with differences in treatment response and growth potential in tumor populations, and 4) the importance of single cell profiling of tumor samples to understand the interplay of the immune system and the tumor during tumor evolution and immunotherapy.

 

10:30 AM   Dissecting cancer heterogeneity through epigenomic variability and transcriptome analysis. W. Greenleaf. Stanford Univ.

11:00 AM   Characterization of tumor microenvironment in breast carcinoma using scRNA-seq. E. Azizi. Mem Sloan Kettering Cancer Ctr, New York.

11:30 AM   Multiplexed and quantitative analysis of tumor suppressor and oncogene function in vivo. M. Winslow. Stanford Univ.

12:00 PM   Detecting clonal populations and constructing cell lineages of complex populations. D. Craig. Univ Southern California, Los Angeles.


Wednesday, October 17

4:15 PM–5:45 PM

Concurrent Platform Session B

24. Variant Interpretation Practices and Resources

Ballroom 20A, Upper Level, San Diego Convention Center

Moderators: Gillian Hooker, Concert Genet, Franklin
  Bruce Korf, Univ Alabama Birmingham

 

41/4:15 Yeast surrogate genetic approaches for functional predictions of genetic variants related to inborn errors of metabolism. A. Sirr, A. Scott, G. Cromie, M. Heyesus, A. El-Hattab, F. Alkuraya, A. Dudley.

42/4:30 Variant interpretation practice amongst clinical genetic counselors: Assessment of training and resource needs to support clinical practice. K.E. Wain, D.R. Azzariti, J. Goldstein, A. Knight Johnson, P. Krautscheid, J.M. O'Daniel, D. Ritter, J.M. Savatt, C.L. Martin, E.R. Riggs, on behalf of the ClinGen Education Working Group.

43/4:45 Variants unmasked by recurrent deletions modify disease presentations of genomic disorders. B. Yuan, W. Bi, N.A. Batzir, S. Gu, W. Zhu, F. Bocanegra, C. Fong, J. Holder, J. Nguyen, J. Zhang, C. Shaw, C. Schaaf, C. Eng, Y. Yang, P. Liu.

44/5:00 GeneMatcher: Analysis of five years of experience. N. Sobreira, E. Wohler, F. Schiettecatte, R. Martin, Z. Akdemir, S. Jhangiani, J. Posey, J. Lupski, D. Valle, A. Hamosh.

45/5:15 ClinGen allele and evidence registries catalyze the emergence of an open ecosystem of variant data and knowledge. R.Y. Patel, P. Pawliczek, L. Babb, A.R. Jackson, S. Paithankar, L.R. Ashmore, C. Bizon, T. Nelson, B. Powell, R. Freimuth, N. Shah, M.W. Wright, S. Dwight, J. Zhen, P. McGarvey, H.L. Rehm, C. Bustamante, S.E. Plon, A. Milosavljevic.

46/5:30 A rigorous interlaboratory examination of the need to confirm NGS-detected variants in clinical genetic testing. S. Lincoln, R. Truty, C. Lin, J. Zook, J. Paul, V. Ramey, M. Salit, H. Rehm, R. Nussbaum, M. Lebo.


Wednesday, October 17

4:15 PM–5:45 PM

Concurrent Platform Session B

25. Integrated Variant Analysis in Cancer Genomics

Ballroom 20BC, Upper Level, San Diego Convention Center

Moderators: Erica Andersen, Univ Utah/ARUP Lab, Salt Lake City
  Steven Harrison, Harvard Med Sch, Cambridge

 

47/4:15 Integrated germline and somatic analysis identifies clinically actionable cancer predisposing pathogenic germline variants in patients with lung cancers. S. Mukherjee, P. Srinivasan, C. Bandlamudi, Y. Kemel, A. Zehir, D.L. Mandelker, M. Walsh, M. Zauderer, M.D. Hellmann, M.E. Selvan, Z.H. Gümüs, S.M. Lipkin, M. Ladanyi, D.B. Solit, M. Robson, L. Zhang, J. Vijai, D. Jones, C. Rudin, B. S. Taylor, Z.K. Stadler, M.F. Berger, K. Offit.

48/4:30 Assessing causality of pathogenic and likely pathogenic germline variants by integrating somatic and germline sequencing in children with cancer enrolled on the “Genomes for Kids” (G4K) sequencing study at St. Jude Children’s Research Hospital. C. Kesserwan, K. Hamilton, S. Newman, E. Quinn, R. McGee, R. Nuccio, S. Hines-Dowell, L. Harrison, S. Brady, M. Rusch, J. Nakitandwe, JM. Valdez, A. Ouma, E. Gerhardt, L. Taylor, S. Foy, A. Silkov, A. Patel, M. Edmonson, D. Hedges, S. Shurtleff, E. Azzato, DW. Ellison, J. Downing, J. Zhang, K. Nichols.

49/4:45 Beyond FISH and karyotype: Complex genomic rearrangements uncovered by clinical mate-pair sequencing in B-lymphoblastic leukemia/lymphoma. C.J. Zepeda Mendoza, S.A. Smoley, S.H. Johnson, J.B. Smadbeck, L.B. Baughn, P.T. Greipp, G. Vasmatzis, N.L. Hoppman, R.P. Ketterling.

50/5:00 Pan-cancer analyses of germline and somatic mitochondrial DNA mutations in pediatric malignancies. X. Gai, P. Triska, K. Kaneva, D. Merkurjev, M.J. Falk, J.A. Biegel.

51/5:15 Experience with germline confirmation for TP53 variants identified by tumor-only sequencing in pediatric cohorts. M. Luo, F. Lin, G. Akgumus, D. Gallo, X. Zhao, H. Jung, J. Tang, E. Romasko, L. Conlin, G. Wertheim, L. Surrey, M. Li.

52/5:30 Sequencing of whole genome, exome and transcriptome for pediatric precision oncology: Somatic variants and actionable findings from 253 patients enrolled in the Genomes for Kids study. S. Newman, E.M. Azzato, J. Nakitandwe, S. Shurtleff, C. Kesserwan, D. Hedges, S. Foy, A. Silkov, Y. Liu, Y. Liu, S. Brady, J. Gu, M.N. Edmonson, A. Patel, M. Wilkinson, K. Hamilton, R. McGee, E. Quinn, R. Nuccio, L. Harrison, A. Bahrami, J.M. Klco, B. Orr, A. Pappo, G. Robinson, M. Rusch, D.W. Ellison, J.R. Downing, K.E. Nichols, J. Zhang.


Wednesday, October 17

4:15 PM–5:45 PM

Concurrent Platform Session B

26. Gene Discovery and Functional Models of Neurological Disorders

Ballroom 20D, Upper Level, San Diego Convention Center

Moderators: Claudia Carvalho, Baylor Col Medicine, Houston
  Harrison Brand, Massachusetts Gen Hosp, Boston

 

53/4:15 Rare biallelic variants in Deoxyhypusine synthase (DHPS), an enzyme involved in the hypusination of eukaryotic translation initiation factor 5A, are associated with neurodevelopmental delay and seizures. M. Ganapathi, L.R. Padgett, K. Yamada, O. Devinsky, R. Willaert, R. Person, P-Y. Billie Au, J. Tagoe, M. McDonald, D. Karlowicz, Y. Shen, V. Okur, L. Deng, C.A. LeDuc, R.G. Mirmira, M.H. Park, T.L. Mastracci, W.K. Chung.

54/4:30 Mutations in ZFP92, a novel KRAB Zinc-finger Protein, results in an X-linked intellectual disability and mitochondrial dysfunction disorder. C.E. Schwartz, J.W. Norris, M. Harr, A. Orrico, E. Zackai.

55/4:45 Biallelic variants in DYNC1I2 cause syndromic microcephaly with intellectual disability, global developmental delay and dysmorphic facial features. M. Ansar, F. Ullah, A. Darius, A. Lai, S.A. Paracha, M.T. Sarwar, J. Iwaszkiewicz, Z. Agha, L. Pais, E. Falconnet, E. Ranza, F.A. Santoni, V. Zoete, J. Ahmed, P. Makrythanasis, N. Katsanis, C. Walsh, E.E. Davis, S.E. Antonarakis.

56/5:00 De novo mutations in CNOT1, a master regulator of gene expression on DNA, RNA, and protein level, cause neurodevelopmental delay. L.E.L.M. Vissers, S. Geuer, S. Kalvakuri, M. Oud, I. van Outersterp, M. Kwint, D.L. Polla, A. Begtrup, A. Ruiz, J.E.V. Morton, C. Griffith, K. Weiss, C. Gamble, J. Bartley, M. Mori, H. Vernon, K. Brunet, C. Ruivenkamp, P. Kruska, A. Afenjar, K. Nugent, F.L. Raymond, M. Cho, H. van Bokhoven, T. Kleefstra, R. Bodmer, M. Muenke, A.P.M. de Brouwer, the DDD study.

57/5:15 Mutations in FAM50A cause Armfield XLID Syndrome: A spliceosomopathy impacting a global repertoire of transcripts involved in neurodevelopment. K. Khan, Y.R. Lee, K. Armfield-Uhas, J.W. Norris, K. Gripp, K.A. Aleck, C. Li, J. Edward Spence, T. Moreland, C. Skinner, R.E. Stevenson, C.H. Kim, E.E. Davis, C.E. Schwartz.

58/5:30 Exome sequencing identifies a novel gene RNF170 for autosomal recessive hereditary spastic paraplegia. Y. Jamshidi, M. Wagner, I. Gehweiler, S. Bakhtiari, E. Ozkan, R. Maroofian, R. Boostani, E. Ghayoor Karimiani, S. Padilla-Lopez, K. Vill, H. Darvish, D.P.S. Osborn, M.C. Kruer, J. Winkelmann, R. Schüle.


Wednesday, October 17

4:15 PM–5:45 PM

Concurrent Platform Session B

27. Whole Exome and Whole Genome Associations

Room 6A, Upper Level, San Diego Convention Center

Moderators: Cristina Justice, NHGRI, Bethesda
  Tara Matise, Rutgers Univ, Piscataway

 

This session is not eligible for continuing education credit.

 

59/4:15 Genome wide discoveries in 13,000 whole genome sequenced rare disease cases and controls. K.E. Stirrups, on behalf of the NIHR BioResource - Rare Diseases and the 100,000 Genomes Project.

60/4:30 Genetic associations of replication timing reveal chromatin and sequence determinants of DNA replication origin activity in humans. Q. Ding, C. Charvet, J. Hsiao, X. Zhu, F.T. Merkle, R.E. Handsaker, S. Ghosh, K. Eggan, S.A. McCarroll, M. Stephens, Y. Gilad, A.G. Clark, A. Koren.

61/4:45 Characterizing the impact of genetic loss of function in inflammation and pain response. C. Lam, C.R. Bauer, S.A. Pendergrass.

62/5:00 Polygenic localization of disease heritability using functional annotations. O. Weissbrod, F. Hormozdiari, B. van de Geijn, A. Schoech, S. Gazal, Y. Reshef, C. Márquez-Luna, L. O’Connor, H. Finucane, A.L. Price.

63/5:15 Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank. I. Tachmazidou, K. Hatzikotoulas, L. Southam, J.E. Gordillo, V. Haberland, J. Zheng, T. Johnson, M. Koprulu, E. Zengini, J. Steinberg, J.M. Wilkinson, S. Bhatnagar, J. Hoffman, L. Yerges Armstrong, G. Davey Smith, T. Gaunt, R.A. Scott, L. McCarthy, E. Zeggini, arcOGEN Consortium.

64/5:30 Automated annotation for re-analysis of whole exome sequencing data: A pilot study. A. Ferrer, P.H. Duffy, J.A. Johnson, C. Kaiwar, M.A. Meiners, R.M. Moore, M.B. Mundy, G.R. Oliver, D.N. Rider, M.E. Williams, F. Vairo, M.A. Cousin, A. Gupta, J.P.A. Kocher, E.W. Klee.


Wednesday, October 17

4:15 PM–5:45 PM

Concurrent Platform Session B

28. Sequencing-based Diagnostics for Newborns and Infants

Room 6B, Upper Level, San Diego Convention Center

Moderators: Hutton Kearney, Mayo Clinic, Rochester
  Qianyi Ma, Univ Michigan, Ann Arbor

 

65/4:15 NGS gene panel for newborn screening, a case-control study. G.L. Yamamoto, F.P. Vairo, K.M. Rocha, M.L. Magalhães, M.S. Naslavsky, R.S. Honjo, C.A. Kim, R. Giugliani, M.R.S. Passos-Bueno, D.R. Bertola.

66/4:30 Utilization of rapid whole genomic sequencing (rWGS) in hospital intensive care units demonstrates a significant improvement in clinical care, healthcare costs and diagnostic rate across a diverse range of patient phenotypes. S.A. Nahas, S. Chowdhury, J. Friedman, J. Gleeson, Y. Ding, M. Wright, M. Tokita, K. Ellsworth, N. Sweeney, D. Dimmock, S. Kingsmore.

67/4:45 Next generation children project: Whole genome sequencing for rapid diagnosis of severely ill children in intensive care. F.L. Raymond, C. French, H. Dolling, A. Sanchis-Juan, I. Delon, E. Dewhurst, T. Austin, R. Armstrong, G. Belteki, M. Bohatschek, S. Bowdin, R.G. Branco, S. Broster, H. Firth, S. Park, A. Parker, C.G. Woods, S. Abbs, D. Rowitch, NIHR BioResource - Rare Diseases.

68/5:00 Rapid exome testing of 500 acutely ill newborns and infants provides equivalent diagnostic sensitivity to whole-genome sequencing. J. Juusola, D. Copenheaver, S. Yang, J. Hare, E. Butler, S. Bale, J. Scuffins, B.D. Solomon, K. Retterer.

69/5:15 The impact of newborn genomic sequencing on families: Findings from the BabySeq Project. S. Pereira, D. Petersen, J.O. Robinson, L. Frankel, K.D. Christensen, S.E. Waisbren, I.A. Holm, A.H. Beggs, R.C. Green, A.L. McGuire, The BabySeq Project Team.

70/5:30 Genomic sequencing (GS) in the neonatal intensive care unit (NICU) demonstrates a significant disease burden in acutely ill infants: Interim results of the NSIGHT2 study. D.P. Dimmock, M.N. Bainbridge, S. Batalov, W. Benson, J.A. Cakici, J. Carroll, S. Caylor, S. Chowdhury, M.M. Clark, C. Clarke, Y. Ding, K. Ellsworth, M. Gaughan, L. Farnaes, A. Hildreth, S. Nahas, L. Salz, E. Sanford, N.M. Sweeney, M. Tokita, N. Veeraraghavan, K. Watkins, K. Wigby, T. Wong, M. Wright, S.F. Kingsmore, RCIGM Investigators.


Wednesday, October 17

4:15 PM–5:45 PM

Concurrent Platform Session B

29. Omics Studies in Alzheimer's Disease

Room 6C, Upper Level, San Diego Convention Center

Moderators: Jonathan Haines, Case Western Reserve Univ, Cleveland
  Morgan Kleiber, UCSD

 

This session is not eligible for continuing education credit.

 

71/4:15 Fine-mapping of Alzheimer's disease risk loci to identify potential novel drug targets. J.Z. Liu, J. Schwartzentruber, K.D. Nguyen, S. Cooper, E. Bello, B.C. Grabiner, J.C. Barrett, T. Johnson, A.R. Bassett, K. Estrada.

72/4:30 Using RNA-sequencing to compare the transcriptional profile of primary human microglia and in-vitro microglial models. F. Calvert, A. Young, N. Kumasaka, A. Knights, N. Murphy, C. McMurran, M. Segel, P. Hutchinson, R. Franklin, D. Gaffney.

73/4:45 Transcriptomic meta-analysis identifies sex-specific and APOE-specific gene signatures in Alzheimer's disease using single gene and network approaches. M. Paranjpe, K. Zalocusky, A. Taubes, M. Sirota.

74/5:00 Brain somatic mutations in Alzheimer’s disease are associated with dysregulated phosphorylation of Tau and aging. J.S. Park, J.H. Lee, E.S. Jung, J.H. Lee.

75/5:15 Decoding the genomic architecture of LOAD using single cells analyses. J. Barrera, L. Song, A. Safi, G.E. Crawford, O. Chiba-Falek.

76/5:30 Identification of distinct immune cell-types associated with restricting development of Alzheimer’s disease from fresh human brains. Y. Kim, J. Fullard, Y. Wang, K. Beaumont, R. Sebra, P. Roussos.


Wednesday, October 17

4:15 PM–5:45 PM

Concurrent Platform Session B

30. Cardiac, Valvular, and Vascular Disorders

Room 6D, Upper Level, San Diego Convention Center

Moderators: Nabila Bouatia-Naji, INSERM/Paris Cardiovasc Res Ctr, France
  Mete Civelek, Univ Virginia, Charlottesville

 

77/4:15 Deep learning of cardiac morphology from UK Biobank MRI data reveals genome-wide associations for bicuspid aortic valve. A. Cordova-Palomera, J. Fries, P. Varma, V.S. Chen, M. Fiterau, K. Xiao, H. Tejeda, B. Keavney, H.J. Cordell, E. Ashley, J.R. Priest.

78/4:30 RERE deficiency leads to downregulation of Gata4 and the development of ventricular septal defects. B. Kim, H. Zaveri, V. Jordan, A. Hernández-García, D. Scott.

79/4:45 PALMD calcific aortic valve stenosis risk variant disrupts a NFATC2 binding site at distant-acting enhancer and activates a fibrogenic program. M. Rosa, M.C. Boulanger, A. Chignon, M. Lamontagne, R. Devillers, G. Mkannez, D. Argaud, G. Rhéaume, N. Gaudreault, S. Thériault, Y. Bossé, P. Mathieu.

80/5:00 Down-regulation of Sox7 impairs epithelial-to-mesenchymal transition and endocardial cushion morphogenesis. A. Hernandez-Garcia, M. Wat, R. Udan, A. Renwick, Z. Yu, C. A. Shaw, M.E. Dickinson, Y. Li, D. A. Scott.

81/5:15 Rational therapeutic epigenetic modulation in the treatment of syndromic thoracic aortic aneurysm. B.E. Kang, R. Bagirzadeh, D. Bedja, H.C. Dietz.

82/5:30 Whole genome sequencing of Kyrgyz highlanders reveals novel insight into the genetic basis of high altitude pulmonary hypertension. T. Stobdan, A. Iranmehr, D. Zhou, O. Poulsen, K. Strohl, A. Aldashev, A. Telenti, H.M. Wong, E. Kirkness, J.C. Venter, V. Bafna, G.G. Haddad.


Wednesday, October 17

4:15 PM–5:45 PM

Concurrent Platform Session B

31. Natural Selection and Human Phenotypes

Room 6E, Upper Level, San Diego Convention Center

Moderators: Michelle Kim, Georgia Inst Tech, Atlanta
  Jazlyn Mooney, UCLA

 

NOTE: Overflow seating for this session is available in Rooms 7A and 7B.

 

83/4:15 Building genealogies for tens of thousands of individuals genome-wide identifies evidence of directional selection driving many complex human traits. S.R. Myers, L. Speidel.

84/4:30 FADS1 and the timing of human adaptation to agriculture. I. Mathieson, S. Mathieson.

85/4:45 The impact of modern human specific sites on human phenotypes. C.R. Robles, S. Sankararaman.

86/5:00 Using high-throughput functional assays of protein variants to advance evolutionary inference of deleterious variants. A.G. Clark, R. Fragoza, H. Yu.

87/5:15 Whole genome sequencing reveals ancient African substructure and local adaptation. S. Fan, M.E.B. Hansen, M.H. Beltrame, A. Ranciaro, E. Mbunwe, J. Chan, A.K. Njamnshi, C. Fokunang, S.W. Mpoloka, G.G. Mokone, T. Nyambo, D.W. Meskel, Y.S. Song, S.A. Tishkoff.

88/5:30 The genetic prehistory of the Andean highlands 7,000 years BP though European contact. J. Lindo, R. Haas, C. Hofman, M. Apata, M.. Moraga, R. Verdugo, J. Watson, C. Llave, D. Witonsky, E. Pacheco, M. Vilena, R. Soria, C. Beall, C. Warinner, J. Novembre, M. Aldenderfer, A. Di Rienzo.


Wednesday, October 17

4:15 PM–5:45 PM

Concurrent Platform Session B

32. Genetics of Cardiometabolic Traits

Room 6F, Upper Level, San Diego Convention Center

Moderators: Amit Khera, Broad Inst, Cambridge
  Yang Luo, Brigham & Women's Hosp & Harvard Med Sch, Boston

 

89/4:15 Meta-analysis in 283,579 East Asians identifies 28 new loci associated with type 2 diabetes. C.N. Spracklen, X. Sim, Y.J. Kim, M. Horikoshi, on behalf of the AGEN and DIAMANTE consortia.

90/4:30 MultiMuTHER – A longitudinal multi-omic study of whole blood gene expression and metabolite levels enabling integrative analysis of multi-omics with genetics and phenotypic trajectories. J.S. El-Sayed Moustafa, M. Abdalla, Y. Jiao, G. Leday, M. Stevens, C. Menni, G. Nicholson, C. Holmes, T.D. Spector, M.I. McCarthy, S. Richardson, E.T. Dermitzakis, K.S. Small.

91/4:45 Large-scale GWAS of human plasma metabolome. P. Surendran, I.D. Stewart, on behalf of the mGAP (metabolome Genetic Architecture Programme) Investigators.

92/5:00 Obesity represses mitochondrial transcriptional activity in human adipose tissue. Z. Miao, M. Alverez, Y. Bhagat, K.L. Mohlke, T. Tusie-Luna, C. Aguilar-Salinas, M. Laakso, P. Pajukanta.

93/5:15 Using genetics to test the phenotypic consequences of higher adiposity uncoupled from its adverse metabolic effects. T.M. Frayling, Y. Ji, S.E. Jones, R. Beaumont, M.A. Tuke, J. Harrison, K.S. Ruth, A. Murray, R. Freathy, M.N. Weedon, A.R. Wood, H. Yaghootkar, J. Tyrrell.

94/5:30 Tissue-wise sub-typing of complex trait based on genetics. A. Majumdar, N. Cai, C. Giambartolomei, H. Shi, J. Flint, B. Pasaniuc.


Wednesday, October 17

6:00 PM–7:00 PM

Concurrent Platform Session C

33. Characterization of Structural Variation in Population Controls and Disease

Ballroom 20A, Upper Level, San Diego Convention Center

Moderators: Nicholas Katsanis, Duke Univ, Durham
  Arvis Sulovari, Univ Washington, Seattle

 

95/6:00 Refining the map of genomic disorder loci and associated driver genes by integrating microarray data from 102,257 genomes and exome sequencing of 37,269 individuals. R.L. Collins, K. Mohajeri, J. Kosmicki, F.K. Satterstrom, J. Wang, J.Y. An, J. Buxbaum, D. Cutler, B. Devlin, S. Sanders, K. Roeder, H. Brand, M. Daly, M.E. Talkowski, The Autism Sequencing Consortium.

96/6:15 Structural variation across human populations and families in more than 37,000 whole-genomes. W. Salerno, A. Carroll, F.J. Sedlazeck, O. Krasheninina, G. Jun, A. Mansfield, J. Farek, Z. Khan, V. Menon, G. Metcalf, E. Boerwinkle, R.A. Gibbs.

97/6:30 Mapping and characterization of structural variation in 23,559 deeply sequenced human genomes. I.M. Hall, H.J. Abel, D. Larson, C. Chiang, R. Layer, A. Regier, K. Kanchi, I. Das, N. Stitziel.

98/6:45 CNVs cause autosomal recessive genetic diseases with or without involvement of SNVs. W. Bi, L. Wang, P. Liu, C. Shaw, H. Dai, L. Cooper, F. Xia, R. Xiao, X. Wang, L. Meng, A. Braxton, P. Ward, S. Peacock, F. Vetrini, W. He, T. Chiang, D. Muzny, R.A. Gibbs, A.L. Beaudet, A. Breman, J. Smith, S.W. Cheung, C. Bacino, C.M. Eng, Y. Yang, J.R. Lupski, B. Yuan.


Wednesday, October 17

6:00 PM–7:00 PM

Concurrent Platform Session C

34. Reanalysis of Sequencing Data to Increase Diagnostic Yield

Ballroom 20BC, Upper Level, San Diego Convention Center

Moderators: Dan Bellissimo, Magee Women's Hosp, Pittsburgh
  Marina DiStefano, Harvard Partners Lab Molec Med, Cambridge

 

99/6:00 Assessing variants in genes of unknown significance: The quest for novel gene discoveries at the NIH Undiagnosed Diseases Program. C. Lau, E. Macnamara, B. Pusey, N. Balanda, P. Kendrick, M. Malicdan, C. Toro, C. Tifft, W. Gahl, UDN. Undiagnosed Diseases Network, D. Adams.

100/6:15 Iterative reanalysis provides diagnostic avenue for previously unsolved rare and complex disease cases. M. Velinder, J. Carey, L. Botto, R. Layer, B. Pedersen, A. Farrell, A. Andrews, P. Bayrak-Toydemir, R. Mao, A. Quinlan, G. Marth.

101/6:30 Description of a systematic approach for the reanalysis of clinical whole exome sequencing data. H. Alsharhan, I. Ward, H. Ayoubieh, C. Applegate, F. Schiettecatte, D. Valle, A. Hamosh, N. Sobreira.

102/6:45 Molecular diagnostic and clinical genomics outcomes of post-reporting reanalysis of exome data over time. P. Liu, L. Meng, E.A. Normand, F. Xia, A. Ghazi, J. Rosenfeld, P. Magoulas, A. Braxton, P. Ward, H. Dai, B. Yuan, W. Bi, R. Xiao, X. Wang, T. Chiang, F. Vetrini, W. He, H. Cheng, J. Dong, C. Gijavanekar, V.R. Sutton, A.L. Beaudet, D. Muzny, R.A. Gibbs, J.E. Posey, S. Lalani, C. Shaw, C.M. Eng, J.R. Lupski, Y. Yang, Additional coauthors will appear in the presentation.


Wednesday, October 17

6:00 PM–7:00 PM

Concurrent Platform Session C

35. Subclonal Somatic Mutations

Ballroom 20D, Upper Level, San Diego Convention Center

Moderators: Sunita Setlur, Brigham & Women's Hosp, Boston
  Dmitriy Sonkin, NCI, Rockville

 

This session is not eligible for continuing education credit.

 

103/6:00 Association of clonal hematopoiesis of indeterminate potential with adverse outcomes in a diverse hospital-based biobank. K.T. Nead, K.N. Maxwell, B. Wubbenhorst, R.L. Kember, J. Renae, M. Levin, H. Williams, D. Birtwell, D.J. Rader, S.M. Damrauer, K.L. Nathanson.

104/6:15 Human glioblastoma arises from the subventricular zone harboring low-level driver mutations. J.H. Lee, J.E. Lee, J.Y. Kahng, S.H. Kim, S.J. Yoon, J.Y. Um, W.K. Kim, J.S. Park, J.K. Lee, J. Park, E.H. Kim, J.H. Lee, J. H. Lee, W.S. Chung, Y.S. Ju, S.H. Park, J.H. Jang, S.G. Kang, J.H. Lee.

105/6:30 Somatically acquired variants contaminate public germline variant population databases. B. Coffee, H. Cox, M. Jones, J.P. De La O., S. Manley, L. Esterling, K. Bowles, B. Roa.

106/6:45 Driving mosaicism: Presence of somatic driver variants in population databases and effect on rare Mendelian diseases. V. Avramovic, M. Brkic, M. Tarailo-Graovac.


Wednesday, October 17

6:00 PM–7:00 PM

Concurrent Platform Session C

36. Diverse Approaches for Identifying Target Genes from GWAS Results

Room 6A, Upper Level, San Diego Convention Center

Moderators: Jason Torres, Univ Oxford, UK
  Francesca Luca, Wayne State Univ, Detroit

 

107/6:00 An integrated approach to functionally characterize GWAS. A.C. Joslin, D.R. Sobreira, G. Hansen, N.J. Sakabe, I. Aneas, L. Montefiori, D. Lehman, M. Nobrega.

108/6:15 Simultaneous analysis of open chromatin, promoter interactions and gene expression across a 24hr period in primary T-cells implicates GWAS SNPs with causal genes. J. Yang, A. McGovern, P. Martin, K. Duffus, M. Imran, P. Fraser, M. Rattray, S. Eyre.

109/6:30 Chromatin structure guided approach to evaluate genetic risk reveals oligodendrocyte intrinsic genetic contribution to multiple sclerosis. O. Corradin, D.C. Factor, P.A. Hall, S. Nisraiyya, A. Barbeau, P.C. Scacheri, P.J. Tesar.

110/6:45 Functional annotation of IBD GWAS loci by enrichment analysis of differentially expressed genes identifies loci with shared biological effects and defines individual genetic immune landscapes. R. Kosoy, A. Hart, A.F. Di Narzo, S. Huang, K. Hao, H. Irizar, B. Losic, A. Castillo, J. Rogers, A. Atreja, A. Hurley, L.A. Peters, J.R. Friedman, F. Baribaud, C. Monast, C. Brodmerkel, S. Plevy, J.F. Colombel, M. Dubinsky, J. Cho, B.E. Sands, E.E. Schadt, A. Kasarskis, C.A. Argmann, M. Suarez-Farinas.


Wednesday, October 17

6:00 PM–7:00 PM

Concurrent Platform Session C

37. From GWAS to Function in Cancer

Room 6B, Upper Level, San Diego Convention Center

Moderators: Semanti Mukherjee, Memorial Sloan Kettering Cancer Ctr, New York
  Kara Maxwell, Univ Pennsylvania, Philadelphia

 

111/6:00 Functional characterization of the 14q24 renal cancer susceptibility locus implicates SWI/SNF complex member DPF3. L. Machado Colli, L. Jessop, T. Myers, M. Machiela, J. Choi, M. Purdue, K. Yu, K. Brown, S. Chanock.

112/6:15 Prostate cancer risk SNP rs10993994 is a trans-eQTL for SNHG11 mediated through MSMB. M. Bicak, X. Wang, X. Gao, M. Middha, R.J. Klein.

113/6:30 Functional analysis revealed a prostate-cancer risk associated germline variant that modulates PSA activity and glycosylation. S. Srinivasan, A. Buckle, The PRACTICAL Consortium, The APCB, J. Clements, J. Batra.

114/6:45 Chromatin interactome mapping identifies target genes at 147 independent breast cancer risk signals. S.L. Edwards, H. Sivakumaran, J. Beesley, M.M. Marjaneh, K.M. Hillman, S. Kaufmann, L. Fachal, D.F. Easton, A.M. Dunning, G. Chenevix-Trench, J.D. French.


Wednesday, October 17

6:00 PM–7:00 PM

Concurrent Platform Session C

38. Insights from and into Mendelian Disorders of the Liver and Pancreas

Room 6C, Upper Level, San Diego Convention Center

Moderators: William T. Gibson, British Columbia Children's Hosp, Vancouver, Canada
  Jennifer L. Cohen, Children's Hosp Philadelphia

 

This session is not eligible for continuing education credit.

 

115/6:00 Identification of a missense variant in the WFS1 gene that causes a mild form of Wolfram syndrome and is also associated with risk for type 2 diabetes in Ashkenazi Jewish individuals. V. Bansal, B.O. Boehm, A. Darvasi.

116/6:15 Mendelian form of nonalcoholic fatty liver disease and/or dyslipidemia due to monoallelic ABHD5 mutations. L. Youssefian, H. Vahidnezhad, AH. Saeidian, S. Pajouhanfar, A. Touati, S. Sotoudeh, P. Mansouri, S. Zeinali, MA. Levine, K. Peris, R. Colombo, J. Uitto.

117/6:30 Bi-allelic mutations in Phe-tRNA synthetase identified from four families are associated with a multi-system disease and support ex-translational function. Z. Xu, W.S. Lo, D.B. Beck, L. Schuch, M. Oláhová, R. Kopajtich, Y.E. Chong, C.L. Alston, E. Seidl, L. Zhai, D. Timchak, C.A. LeDuc, A.C. Borczuk, A.F. Teich, J. Juusola, C. Sofeso, C. Müller, G. Pierre, T. Hilliard, P.D. Turnpenny, M. Wagner, M. Kappler, F. Brasch, J.P. Bouffard, L.A. Nangle, R.W. Taylor, H. Prokisch, M. Griese, W.K. Chung, P. Schimmel.

118/6:45 RINT1 biallelic alterations: A novel cause of infantile onset recurrent liver failure with dysostosis multiplex. M.A. Cousin, E. Conboy, J.S. Wang, D. Lenz, M. Williams, T.L. Schwab, R.S. Abraham, S. Barnett, M. El-Youssef, R. Graham, L.H. Gutierrez Sanchez, L. Hasadsri, G.F. Hoffmann, N.C. Hull, R. Kopajtich, R. Kovacs-Nagy, J. Li, D. Marx-Berger, V. McLin, H. Prokisch, D. Rymen, C. Staufner, Y. Yang, K.J. Clark, B.C. Lanpher, E.W. Klee.


Wednesday, October 17

6:00 PM–7:00 PM

Concurrent Platform Session C

39. Scalable Tools to Enable Collaboration and Reproducible Analyses

Room 6D, Upper Level, San Diego Convention Center

Moderators: Nara Sobreira, Johns Hopkins Univ, Baltimore
  Andrew Marderstein, Cornell Univ, Ithaca

 

119/6:00 Scalable and accurate implementation of generalized mixed model for region-based association tests in large biobanks and cohorts. W. Zhou, J.B. Nielsen, L.G. Fritsche, J. LeFaive, M.B. Elvestad, K. Hveem, G.R. Abecasis, C.J. Willer, S. Lee.

120/6:15 Analyzing the world’s largest public human variation resources in less than a day: Massively scalable software for genomic analysis. T. Poterba, L. Abbott, J. Bloom, C. Churchhouse, R. Cownie, L.C. Francioli, J. Goldstein, D. Howrigan, K.J. Karczewski, D. King, D. Palmer, P. Schultz, G. Tiao, R. Walters, A. Wang, D.G. MacArthur, B.M. Neale, C. Seed.

121/6:30 Kipoi: Accelerating the community exchange and reuse of predictive models for regulatory genomics. J. Gagneur, Z. Avsec, R. Kreuzhuber, J. Israeli, N. Xu, J. Cheng, A. Shrikumar, L. Urban, D. Kim, W.H. Ouwehand, A. Kundaje, O. Stegle.

122/6:45 DRAMS: A tool to Detect and Re-Align Mixed-up Samples leveraging multi-omics data. Y. Jiang, Y. Xia, L. Han, G. Giase, K. Grennan, L. Sloofman, S. Liu, C. Chen, B. Li, C. Liu.


Wednesday, October 17

6:00 PM–7:00 PM

Concurrent Platform Session C

40. Genomic Testing: Strategies and Patient Perspectives

Room 6E, Upper Level, San Diego Convention Center

Moderators: Colleen A. Campbell, Univ Iowa, Iowa City
  Amy A. Lemke, North Shore Univ Hlth Sys, Evanston

 

NOTE: Overflow seating for this session is available in Rooms 7A and 7B.

 

123/6:00 Patient-data sharing of whole exome sequencing results with GenomeConnect informs variant interpretation and gene-disease relationships. J. M. Savatt, D. R. Azzariti, E. Palen, J. Hart, B. L. Kattman, M. J. Landrum, S. M. Harrison, V. Rangel Miller, J. Rhode, J. A. Vidal, D. H. Ledbetter, H. Rehm, W. A. Faucett, E. R. Riggs, C. L. Martin.

124/6:15 Blood biospecimen donation and consent to share data among African American women. C. Wang, L. Barber, L. Rosenberg, J.R. Palmer.

125/6:30 Effectiveness of the Genomics ADvISER decision aid for the selection of incidental genome sequencing results: Randomized clinical trial. Y. Bombard, M. Clausen, C. Mighton, S. Shickh, S. Casalino, T.H.M. Kim, L. Carlsson, E. Joshi, L. McCuaig, N. Baxter, A. Scheer, C. Elser, A. Eisen, M. Evans, R.H. Kim, S. Panchal, T. Graham, M. Aronson, C. Piccinin, L. Winter-Paquette, K. Semotiuk, J. Lerner-Ellis, J.C. Carroll, J. Hamilton, E. Glogowski, K. Schrader, K. Offit, M. Robson, K. Thorpe, A. Laupacis.

126/6:45 Canadian indigenous peoples & genomics: Starting a conversation. P.H. Birch, R.R. Coe, R. Lesueur, R. Kenny, N. Makela, R. Price, W.H. McKellin, A. Lehman, J. Morgan.


Wednesday, October 17

6:00 PM–7:00 PM

Concurrent Platform Session C

41. Therapeutic Development: Adding or Subtracting

Room 6F, Upper Level, San Diego Convention Center

Moderators: Hal Dietz, Johns Hopkins Univ Sch Med, Baltimore
  Anna Lindstrand, Karolinska Inst, Stockholm, Sweden

 

127/6:00 Retinal phenotype correction by gene therapy in the novel Mfrp mouse model of a human ophthalmic syndrome. M. Voronchikhina, A. Chekuri, B. Sahu, V.R.M. Chavali, A.N. Alapati, J.C. Zenteno, M.M. Jablonski, R. Ayala-Ramirez, A. Dinculescu, S. Borooah, R. Ayyagari.

128/6:15 One size fits all: Transcriptional upregulation of a disease modifier gene as a mutation-independent approach in muscular dystrophy. D.U. Kemaladewi, P.S. Bassi, R. Kember, K. Lindsay, E. Hyatt, E.A. Ivakine, R.D. Cohn.

129/6:30 AAV gene therapy with artificial miRNA-mediated oligodendrocyte-specific gene suppression: Implication for the treatment of Pelizaeus-Merzbacher disease with PLP1 duplication. K. Inoue, H. Li, H. Okada, T. Okada, Y. Goto.

130/6:45 CRISPR/Cas9 single guide treatment of novel multi-exon duplication mouse model of Duchenne muscular dystrophy removes 139kbp duplication and restores full length dystrophin. D. Wojtal, E. Hyatt, K. Lindsay, E.A. Ivakine, R.D. Cohn.


Thursday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session D

42. Advances in GWAS Analytical Methods

Ballroom 20A, Upper Level, San Diego Convention Center

Moderators: Yasmmyn Salinas, Yale Sch Public Hlth, New Haven
  Alper Uzun, Alpert Med Sch, Brown Univ, Providence

 

131/9:00 Efficient cross-trait penalized regression increases prediction accuracy in large cohorts using secondary phenotypes. W. Chung, J. Chen, C. Turman, S. Lindstrom, Z. Zhu, P. Loh, P. Kraft, L. Liang.

132/9:15 Association studies for all: A novel framework to allow for the well-calibrated genomic analysis of underrepresented admixed individuals. E.G. Atkinson, A.X. Maihofer, A.R. Martin, K.C. Koenen, B.M. Neale, C.M. Nievergelt, M.J. Daly.

133/9:30 Reversing GWAS to identify and model genetic subtypes. A. Dahl, N. Cai, A. Ko, C. Gignoux, M. Laakso, E. Burchard, P. Pajukanta, J. Flint, N. Zaitlen.

134/9:45 Wavelet screaming: A novel approach to analyzing GWAS data. W. Denault, J. Juodakis, B. Jacobsson, A. Jugessur, H. Gjessing.

135/10:00 PASTRY (A method to avoid Power ASymmeTRY): Achieving balanced power for detecting risk and protective alleles in meta-analysis of association studies with overlapping subjects. E. Kim, B. Han.

136/10:15 Meta-MultiSKAT: Region-based rare variant meta-analysis of multiple phenotypes using summary statistics. D. Dutta, S.A. Gagliano, J. Weinstock, M. Zawistowski, F. Cucca, D. Schlessinger, G. Abecasis, C. Brummett, S. Lee.


Thursday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session D

43. Genomic Insights from Diverse Populations

Ballroom 20BC, Upper Level, San Diego Convention Center

Moderators: Timothy Thornton, Univ Washington, Seattle
  Eimear Kenny, Mount Sinai Sch Med, New York

 

137/9:00 TOPMed based imputation in minority samples. M.H. Kowalski, H. Qian, Z. Hou, J.D. Rosen, L.M. Raffield, R. Kaplan, E. Boerwinkle, K.E. North, C. Kooperberg, J.G. Wilson, A.P. Reiner, Y. Li, on behalf of the TOPMed Hematology and Hemostasis Working Group.

138/9:15 Creating population-specific reference panels for improved genotype imputation. J.C. Carlson, N.L. Hawley, G. Sun, H. Cheng, T. Naseri, M.S. Reupena, R. Deka, S.T. McGarvey, R.L. Minster, D.E. Weeks, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium.

139/9:30 The global landscape of pharmacogenomic variation. C. Gignoux, E. Sorokin, G. Wojcik, G. Belbin, S. Bien, N. Abul-Husn, P. Norman, C. Hodonsky, J. Odgis, H. Highland, C. Avery, S. Buyske, T. Matise, K. Barnes, B. Hailu, J.L. Ambite, K. North, R. Loos, C. Haiman, C. Kooperberg, U. Peters, L. Hindorff, C. Carlson, C. Bustamante, E. Kenny, on behalf of the Population Architecture using Genomics and Epidemiology (PAGE) Study.

140/9:45 Transcriptome-based association study in Hispanic cohorts implicates novel genes in lipid traits. A.S. Andaleon, L.S. Mogil, H.E. Wheeler.

141/10:00 A 100,000 Genome project haplotype reference panel of 57,786 haplotypes. S. Shi, S. Hu, S. Myers, J. Marchini.

142/10:15 Identification and characterization of adaptive regulatory variation in diverse human populations. J.J. Vitti, S. Gosai, R. Tewhey, S. Reilly, P.C. Sabeti.


Thursday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session D

44. Comprehensive Descriptions of Genetic Architecture of Rare Diseases

Ballroom 20D, Upper Level, San Diego Convention Center

Moderators: Kym Boycott, Univ Ottawa, Canada
  Laure Fresard, Stanford Univ

 

143/9:00 Insights into effective methods for Mendelian gene discovery from family based genomic analysis of over 22,000 families from worldwide populations. A.H. O'Donnell-Luria, J.E. Posey, J.X. Chong, E.E. Blue, N.L.M. Sobreira, F. López-Giráldez, J. Knight, S. Baxter, J.R. Lupski, D. Valle, A. Hamosh, K. Doheny, D. Avramoupolus, H.L. Rehm, D.G. MacArthur, T.C. Matise, S. Buyske, R.P. Lifton, M. Gunel, S.M. Mane, M.B. Gerstein, D.A. Nickerson, M.J. Bamshad, GSP Coordinating Center & Baylor Hopkins, Broad, Yale and UW Centers for Mendelian Genomics.

144/9:15 The genetic landscape of Diamond-Blackfan anemia. J.M. Verboon, J.C. Ulirsch, S. Kazerounian, D. Yuan, L.S. Ludwig, M.H. Guo, N.J. Abdulhay, C. Fiorini, R.E. Handsaker, G. Genovese, E. Lim, A. Cheng, B. Cummings, K.R. Chao, S. McCaroll, A. O’Donnell, N. Gupta, S.B. Gabriel, D.G. MacArthur, E.S. Lander, M. Lek, L. Da Costa, D.G. Nathan, A. Korostelev, R. Do, H.T. Gazda, V. G. Sankaran, Collaborative DBA Consortium.

145/9:30 Quantifying the contribution of X-linked coding variants to developmental disorders. H.C. Martin, N. Akawi, A. Sifrim, K.E. Samocha, J. Kaplanis, J.F. McRae, M.E. Hurles, the Deciphering Developmental Disorders Study.

146/9:45 WES application in a large cohort of arthrogryposis: Evidence for oligogenic inheritance, and candidate novel disease genes. D. Pehlivan, Y. Bayram, N. Gunes, A. Gezdirici, Z. Coban-Akdemir, J.M. Fatih, T. Yildirim, I.A. Bayhan, A. Bursali, E. Yilmaz-Gulec, E. Karaca, S.N. Jhangiani, D.M. Muzny, R.A. Gibbs, N.H. Elcioglu, J.E. Posey, B. Tuysuz, J.R. Lupski.

147/10:00 Genetic testing of 1346 patients with cerebral palsy reveals a monogenetic cause of disease in one-third of cases, vast genetic heterogeneity, and a significant recurrence risk. F. Millan, H.Z. Elloumi, C. Teigen, J. Scuffins, R.I. Torene, K. Retterer, D.A. McKnight.

148/10:15 Diagnostic yield from WES, WGS and RNA testing among 213 neuromuscular families: Known versus novel disease genes, coding versus non-coding variants. L.B. Waddell, M. Lek, E.C. Oates, R. Ghaoui, G.L. O'Grady, S.A. Sandaradura, B.B. Cummings, E. Valkanas, R. Roxburgh, S. Bryen, A. Bournazos, F. Evesson, J.L. Marshall, K. Chao, K.J. Jones, L. Douglas, M. Rodrigues, M. Davis, N.G. Laing, K.N. North, N.F. Clarke, D.G. MacArthur, S.T. Cooper.


Thursday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session D

45. Learning from Genome Mutation Patterns

Room 6A, Upper Level, San Diego Convention Center

Moderators: Stephane Wenric, Icahn Sch Med Mount Sinai, New York
  Corbin Quick, Univ Michigan, Ann Arbor

 

149/9:00 Mutation rate heterogeneity and selective constraint in 28,000 deep whole genomes. P.J. Short, C. Penkett, K. Stirrups, L.C. Francioli, K.J. Karczewski, K.E. Samocha, D.G. MacArthur, W.H. Ouwehand, J.C. Barrett, M.E. Hurles, on behalf of The NIHR BioResource, the 100,000 Genomes Project RD Pilot, and the gnomAD consortium.

150/9:15 Widespread transcriptional scanning in testes modulates gene evolution rates. B. Xia, M. Baron, Y. Yan, F. Wagner, S. Kim, D. Keefe, J. Alukal, J. Boeke, I. Yanai.

151/9:30 Genome-wide detection and characterization of de novo repeat mutations in healthy trio families. I. Mitra, M. Gymrek.

152/9:45 Deciphering signatures of mutational processes in human germline. V. Seplyarskiy, R. Soldatov, J. Goldmann, P. Kharchenko, C. Gilissen, W. Wong, S. Sunyaev.

153/10:00 Inferring past generation times from changes in the mutation spectrum in human evolution. P. Moorjani, Z. Gao, G. Amster, M. Przeworski.

154/10:15 Insights into the patterns of somatic mutation accumulation in human cancer. K. Akdemir, A. Futreal.


Thursday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session D

46. Neurodegenerative Disease: Revealing Disease Mechanisms

Room 6B, Upper Level, San Diego Convention Center

Moderators: Loyal Goff, Johns Hopkins Univ Sch Med, Baltimore
  Jennifer G. Mulle, Emory Univ Sch Med, Atlanta

 

155/9:00 A small number of single cell transcriptomes stratifies Parkinsonism iPSC dopamine neurons, unravels the modelled disease process and identifies HDAC4 as a regulator of cellular phenotypes in Parkinson’s dopamine neurons. C. Webber, C. Lang, K. Campbell, B. Ryan, P. Carling, M. Attar, J. Vowles, R. Bowden, F. Baig, M. Hu, S. Cowley, R. Wade-Martins.

156/9:15 PARK14 genetically interacts with PINK1 in regulating mitochondrial function and bioenergetics in a Drosophila Parkinson’s disease model. S. Kalvakuri, R. Bodmer.

157/9:30 TP73 is an amyotrophic lateral sclerosis risk gene. J.M. Downie, S.B. Gibson, S. Tsetsou, K.L. Russell, M.D. Keefe, K.P. Figueroa, M.B. Bromberg, L.C. Murtaugh, J.L. Bonkowsky, S.M. Pulst, L.B. Jorde.

158/9:45 Simultaneous genetic analysis of 4,000 traits to identify drug targets for multiple sclerosis. A. Fish, P.G. Bronson, R. Nagy, C. Vangjeli, J. Barrett, G. McVean, K. Estrada, M. Weale, P. Donnelly, S. John.

159/10:00 iPSC-derived neurons carrying FMR1 unmethylated full mutations show signs of neurodegeneration: Large CGG repeat expansions are required for methylation and silencing of the gene. V. Nobile, E. Tabolacci, P. Chiurazzi, G. Neri.

160/10:15 Utilizing gene expression profiles to complement the analysis of genomic modifiers of the clinical onset of Huntington disease. G.E.B. Wright, N.S. Caron, B. Ng, L. Casal, J. Ooi, S. Mostafavi, M.A. Pouladi, C.J.D. Ross, M.R. Hayden.


Thursday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session D

47. DNA Methylation in Human Disease

Room 6C, Upper Level, San Diego Convention Center

Moderators: John Greally, Albert Einstein Col Med, New York
  Charles Mordaunt, UC Davis

 

NOTE: Overflow seating for this session is available in Room 2.

 

161/9:00 Developmental methylomics of childhood trauma and its health consequences. E.J.C.G. van den Oord, R.F. Chan, M. Zhao, L.Y. Xie, E.J. Costello, E. Copeland, K.A. Aberg.

162/9:15 Distinguishing infection from infectious disease using methylation marks comprised within cell-free DNA. A.P. Cheng, P. Burnham, D. Dadhania, J.R. Lee, M. Suthanthiran, I. De Vlaminck.

163/9:30 Promoter GGX repeat expansion and exon 1 methylation of XYLT1 in Baratela-Scott syndrome. A.J. LaCroix, D. Stabley, M.P. Adam, M. Mehaffey, K. Kernan, C. Myers, C. Fagerstrom, G. Anadiotis, Y. Akkari, K. Robbins, M.B. Bober, A. Duker, D. Miller, M. Kircher, M. Bamshad, D. Nickerson, U.W. Center for Mendelian Genomics, K. Sol-Church, H.C. Mefford.

164/9:45 Circulating tumor DNA methylation haplotypes in plasma can detect cancer four years prior to conventional diagnosis. A. Gore, X. Chen, J. Gole, J. Min, Q. He, X. Li, L. Cheng, Z. Zhang, H. Nu, Z. Li, Z. Xie, X. Yang, H. Shi, J. Dang, C. McConnell, J. Zhang, Z. Yuan, J. Wang, M. Lu, W. Ye, Y. Gao, K. Zhang, R. Liu, J. Li.

165/10:00 Blood DNA methylation profiles are altered years before breast cancer diagnosis: Findings from a case-cohort analysis in the Sister Study. Z. Xu, D.P. Sandler, J.A. Taylor.

166/10:15 Genetically predicted methylation biomarkers and prostate cancer risk: A methylome-wide association study in over 140,000 European descendants. L. Wu, Y. Yang, X. Guo, X.O. Shu, Q. Cai, X. Shu, B. Li, R. Tao, M.J. Roobol, G.G. Giles, H. Brenner, E.M. John, J. Clements, E.M. Grindedal, J.Y. Park, J.L. Stanford, Z. Kote-Jarai, C.A. Haiman, R.A. Eeles, W. Zheng, J. Long, the PRACTICAL, CRUK, BPC3, CAPS, PEGASUS consortia*.


Thursday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session D

48. Genetic Disorders of Vision and Hearing

Room 6D, Upper Level, San Diego Convention Center

Moderators: Suzanne Leal, Baylor Col Med, Houston
  Elizabeth Bhoj, Children's Hosp Pennsylvania, Philadelphia

 

167/9:00 Sequence variants associating with corneal structure and diseases. E.V. Ivarsdottir, S. Benonisdottir, F. Jonasson, G. Thorleifsson, P. Sulem, H. Holm, A. Oddsson, U. Styrkarsdottir, S. Kristmundsdottir, U. Thorsteinsdottir, D.F. Gudbjartsson, K. Stefansson.

168/9:15 Biallelic loss-of-function variants in DNMBP cause congenital cataract and visual impairment in human and flies. H. Chung, M. Ansar, R. Taylor, A. Nazeer, S. Imtiaz, M.T. Sarwar, P. Makrythanasis, S. Qureshi, E. Falconnet, M. Guipponi, D. Schlegel, S. Neuhauss, C.J. Pournaras, E. Ranza, F.A. Santoni, J. Ahmed, I. Shah, K. Gul, G. Black, H. Bellen, S.E. Antonarakis.

169/9:30 ABCA4-associated disease as a model for missing heritability in autosomal recessive disorders: Novel non-coding splice, cis-regulatory, structural and recurrent hypomorphic variants. M. Bauwens, A. Garanto, R. Sangermano, S. Naessens, N. Weisschuh, J. De Zaeytijd, M. Khan, F. Sadler, I. Balikova, C. Van Cauwenbergh, T. Rosseel, J. Bauwens, K. de Leeneer, S. De Jaegere, T. Van Laethem, M. De Vries, K. Carss, A. Fakin, G. Arno, A.R. Webster, T. de Ravel de l'Argentière, Y. Sznajer, M. Vuylsteke, S. Kohl, B. Wissinger, T. Cherry, R.W.J. Collin, F.P.M. Cremers, B.P. Leroy, E. De Baere.

170/9:45 GWAS of African populations reveals link between glaucoma and Alzheimer’s disease. M.A. Hauser, R.R. Allingham, C.C. Khor, C.J. Van Der Heide, J.I. Rotter, S.H. Wang, P.W.M. Bonnemaijer, N. Risch, T.J. Hoffman, E. Jorgenson, O. Olawoye, A. Ashaye, C.C.W. Klaver, R.N. Weinreb, A. Ashley-Koch, J.H. Fingert, T. Aung, Eyes of Africa Consortium.

171/10:00 Three novel hearing loss genes reveal previously unrecognized roles of their protein products in the perception of sound. G. Bademci, C. Li, O. Diaz-Horta, C. Abad, B. Vona, R. Maroofian, A. Subasioglu, E. Mihci, O. Alper, B.G. Nur, M. Benham, A. Incesulu, F. Silan, S. Tokgoz-Yilmaz, M. Salehi, T. Haaf, F.B. Cengiz, S.H. Blanton, D. Duman, K. Walz, R.G. Zhai, M. Tekin.

172/10:15 Whole exome sequencing (WES) in infants with congenital hearing loss as a model for genomic newborn screening. D.J. Amor, L. Downie, R.A. Burt, E. Lynch, M. Martyn, Z. Poulakis, C. Gaff, V. Sung, M. Wake, M. Hunter, K. Saunders, S. Lunke, J.L. Halliday.


Thursday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session D

49. Emerging Omics Technologies

Room 6E, Upper Level, San Diego Convention Center

Moderators: Christine R. Beck, Univ Connecticut Hlth Ctr/Jackson Lab Genomic Med, Farmington
  Paola Benaglio, UCSD

 

NOTE: Overflow seating for this session is available in Rooms 7A and 7B.

 

173/9:00 Using untargeted metabolomics and Mendelian randomization to dissect causal relationships in the obesity metabolome. Y.H. Hsu, C.M. Astley, S. Vedantam, J.M. Mercader, A. Metspalu, K. Fischer, K. Fortney, E.K. Morgen, C. Gonzalez, M.E. Gonzalez, T. Esko, J.N. Hirschhorn.

174/9:15 Cross-platform, large-scale genetic discovery of small molecule products of metabolism and application to clinical outcomes. C. Langenberg, C. Li, I. Stewart, L.B.L. Wittemans, C. Oliver-Williams, P. Surendran, E.K. Biggs, R. Bonelli, R.A. Scott, S. Burgess, V. Zuber, A. Koulman, F. Imamura, N.G. Forouhi, K.T. Khaw, J.L. Griffin, A.M. Wood, F.M. Gribble, F. Reimann, M. Bahlo, J. Danesh, A. Butterworth, N.J. Wareham, L. Lotta, MacTel Consortium.

175/9:30 Identification of FXTAS genetic modifiers by combining high-throughput metabolic profiling with fly genetics. H.E. Kong, J. Lim, F. Zhang, L. Huang, D.L. Nelson, P. Jin.

176/9:45 Analysis of 33,527 haploid sperm genomes from 20 individuals reveals new relationships underlying meiotic recombination and aneuploidy. A.D. Bell, C.J. Mello, S.A. McCarroll.

177/10:00 Explaining gene expression: Massively parallel in-silico testing of gene expression regulators reveals large scale patterns of shared and divergent regulation across cancers and tissues. L. Erdman, M. Mai, D. Sokolowski, M. Wilson, A. Goldenberg.

178/10:15 Compositional and Time-course Aware Genetic Analysis (CTG): A novel analysis platform for high-throughput functional genetic interaction screens. B.P. Munson, J. P. Shen, S. Fong, A. Birmingham5, R. Sasik, J.F. Kreisberg, P. Mali, T. Ideker.


Thursday, October 18

9:00 AM–10:30 AM

Concurrent Platform Session D

50. Discovery Studies of Cardiovascular and Metabolic Phenotypes

Room 6F, Upper Level, San Diego Convention Center

Moderators: Jennifer E. Huffman, VA Boston Healthcare System
  Stella Aslibekyan, Univ Alabama Birmingham

 

179/9:00 Genome-wide association studies in >500,000 individuals identify novel loci for coronary artery disease and myocardial infarction. J.A. Hartiala, Y. Han, Q. Jia, P. Huang, N.C. Woodward, J. Gukasyan, L.K. Stolze, Z. Kurt, D-A. Trégouët, N.L. Smith, M. Seldin, C. Pan, M. Mehrabian, A.J. Lusis, W.H.W. Tang, S.L. Hazen, X. Yang, C.E. Romanoski, H. Allayee.

180/9:15 Leveraging whole genome sequencing to identify novel determinants of platelet function. B.A.T. Rodriguez, A.R. Keramati, L. Yanek, M.H. Chen, K. Ryan, B. Gaynor, J.A. Brody, N. Faraday, L. Becker, J. Lewis, A.D. Johnson, R.A. Mathias.

181/9:30 Genome-wide identification of DNA methylation quantitative trait loci in human whole blood highlights novel pathways for cardiovascular diseases. T. Huan, R. Joehanes, C. Song, F. Peng, Y. Guo, M. Mendelson, C. Yao, C. Liu, L. Almli, K. Conneely, A. Johnson, M. Fornage, L. Liang, D. Levy.

182/9:45 Exploring population-specific incidence of disease in a multi-ethnic health system reveals Native American haplotype underlying peripheral artery disease in Dominicans. S.F. Cullina, G.M. Belbin, G.L. Wocjik, E.P. Sorokin, M.A. Levin, C.R. Gignoux, E.E. Kenny.

183/10:00 Identification of structural variation associated with cardiometabolic traits in the Finnish population. L. Chen, L. Ganel, H.J. Abel, D.E. Larson, A. Regier, I. Das, S.K. Service, X. Yin, A.U. Jackson, M.I. Kurki, A.S. Havulinna, P. Palta, S.K. Dutcher, V. Salomaa, C.W.K. Chiang, A. Palotie, S. Ripatti, M. Laakso, N.B. Freimer, M. Boehnke, A.E. Locke, N.O. Stitziel, I.M. Hall, FinMetSeq Consortium.

184/10:15 Identifying novel genes influencing cardiometabolic risk factors from GWAS-identified loci for triglyceride levels using a high-throughput zebrafish screen. B. von der Heyde, M. Masiero, A. Emmanouilidou, T. Klingström, P. Ranefall, C. Wählby, A. Larsson, E. Ingelsson, M. den Hoed.


Thursday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session E

51. What are We Missing? Identification of Previously Underappreciated Mendelian Variants

Ballroom 20A, Upper Level, San Diego Convention Center

Moderators: Daniel C. Koboldt, Nationwide Children's Hosp, Columbus
  Zeynep Coban Akdemir, Baylor Col Medicine, Houston

 

185/11:00 Illuminating the dark genome: Evaluation of technologies to assess medically relevant dark spots. F.J. Sedlazeck, H. Doddapaneni1, D. Kalra, K. Walker, S.N. Jhangiani, S. Richards, Y. Han, Q. Meng, G. Metcalf, W.J. Salerno, E. Boerwinkle, D. Muzny, R.A. Gibbs.

186/11:15 Contribution of retrotransposition to developmental disorders. E.J. Gardner, A. Sifrim, G. Gallone, E. Prigmore, P.J. Short, H.V. Firth, M. E. Hurles, on behalf of the Deciphering Developmental Disorders study.

187/11:30 Mobile element insertions in 28,000 clinical exomes. R.I. Torene, K. Galens, J. Scuffins, B. Friedman, E. Ryan, H. Sroka, A. Singleton, C. Teigen, L.B. Henderson, K.G. Monaghan, J. Juusola, K. Retterer.

188/11:45 GangSTR: Genome-wide genotyping of short tandem repeat expansions. N. Mousavi, S. Shleizer-Burko, M. Gymrek.

189/12:00 Analysis of 5'UTR variation in WGS from over 18,000 individuals identifies highly constrained regulatory elements and a role in human disease. N. Whiffin, K. Karczewski, A. O’Donnell-Luria, S.A. Cook, D.G. MacArthur, J.S. Ware.

190/12:15 Uncovering pathogenic variants in the non-coding genome through the UK 100,000 genomes project. J.M. Ellingford, H. Thomas, G. Arno, A. Webster, G. Beaman, K. Webb, K. Ibanez-Garikano, D. Polychronopoulos, C. Odhams, R. O'Keefe, W.G. Newman, G.C.M. Black.


Thursday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session E

52. Single Cell Approaches to Reveal Disease Biology

Ballroom 20BC, Upper Level, San Diego Convention Center

Moderators: Kimberly Aldinger, Seattle Children's Res Inst
  Manolis Kellis, Massachusetts Inst Technol, Cambridge

 

191/11:00 Single cell transcriptomics of the human airway epithelium reveals cellular and functional changes underlying type 2-high asthma. N.D. Jackson, K.C. Goldfarbmuren, J.L. Everman, S.P. Sajuthi, C. Rios, R. Powell, M. Armstrong, J. Gomez, C. Michel, N. Reisdorph, C. Eng, S.S. Oh, J. Rodriguez-Santana, E.G. Burchard, M.A. Seibold.

192/11:15 Single cell RNASeq of Crohn’s disease tissues defines two cell subset-based signatures of inflammation, predicting treatment responses. J.H. Cho, M. Giri, J. Martin, R. Ungaro, L. S. Chuang, S. Nayar, P. Desai, J. Friedman, C. Whitehurst, J. Hyams, L.A. Denson, S. Kugathasan, A. Greenstein, M. Merad, E. Kenigsberg.

193/11:30 Human lineage tracing enabled by mitochondrial mutations and single cell genomics. L.S. Ludwig, C.A. Lareau, J.C. Ulirsch, E. Christin, C. Muus, A. Brack, T. Law, C. Rodman, O. Rozenblatt-Rosen, M.J. Aryee, J.D. Buenrostro, A. Regev, V.G. Sankaran.

194/11:45 Whole cortical scRNA-seq reveals misregulation in multiple cellular and molecular networks in Fragile X syndrome. E. Donnard, H. Shu, K. Gellatly, A. Derr, P. McDonel, M. Garber.

195/12:00 Chromatin dynamics of cortical organoids at single-cell resolution. R.M. Mulqueen, B.A. DeRosa, A.J. Fields, A.C. Adey, B.J. O'Roak.

196/12:15 The loss of Ret signaling in Hirschsprung disease: Cellular consequences and penetrance. S. Chatterjee, E. Vincent, D. Auer, G. Cannon, L. Goff, A. Chakravarti.


Thursday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session E

53. Expanding the Scope of Mendelian Randomization

Ballroom 20D, Upper Level, San Diego Convention Center

Moderators: Ching-Ti Liu, Boston Univ SPH
  Leyao Wang, Washington Univ, St. Louis

 

197/11:00 Mendelian randomization and procedure-wide associations studies to evaluate the association of obesity with surgical procedures. J.R. Robinson, R.J. Carroll, L. Bastarache, Z. Mou, W. Wei, J. Connolly, H. Hakonarson, F. Mentch, P.K. Crane, S.J. Hebbring, D.R. Gordon, A.S. Gordon, E.A. Rosenthal, I.B. Stanaway, M.G. Hayes, W. Wei, L. Petukhova, B. Namjou, G. Zhang, M.S. Safarova, N.A. Walton, R.J.F. Loos, S.N. Murphy, G.P. Jackson, I.J. Kullo, G.P. Jarvik, E.B. Larson, C. Weng, D. Roden, J.C. Denny.

198/11:15 Mendelian randomization-derived priors substantially improve power of Bayesian GWAS on human lifespan. N. Mounier, P.R.H.J. Timmers, K. Läll, K. Fischer, Z. Ning, X. Feng, A. Bretherick, D.W. Clark, X. Shen, T. Esko, J.F. Wilson, P.K. Joshi, Z. Kutalik.

199/11:30 Identifying the tissue-specific influence of gene expression on neurological and psychiatric traits: A Mendelian randomisation study on gene expression within the human brain. D.A. Baird, J. Liu, S. Sieberts, T. Perumal, J. Zheng, V. Haberland, T. G. Richardson, M. Carrasquillo, M. Allen, J. S. Reddy, P. L. De Jagger, N. Ertekin-Taner, L. M. Mangravite, B. Logsdon, P. Haycock, G. Hemani, G. D. Smith, K. Estrada, T. R. Gaunt, AMP-AD eQTL working group.

200/11:45 The neurodevelopmental 16p11.2 CNVs have a hitherto unappreciated mirror effect on sexual development in humans and animal models. K. Mannik, M. Lepamets, A. Mikhaleva, K. Lepik, T. Arbogast, H. Ademi, Z. Kupchinsky, C. Attanasio, A. Messina, S. Rotman, E. Dubruc, J. Chrast, S. Martin-Brevet, T. Laisk-Podar, Y. Herault, C.M. Lindgren, Z. Kutalik, J.C. Stehle, N. Katsanis, S. Nef, B. Draganski, E.E. Davis, A. Reymond, R. Magi, The 16p11.2 European Consortium, The Simons VIP Consortium, The eQTLGen Consortium.

201/12:00 Mendelian randomization combining GWAS and eQTL data reveals new loci, extensive pleiotropy and genetic determinants of complex and clinical traits. E. Porcu, S. Rüeger, F.A. Santoni, A. Reymond, Z. Kutalik, eQTLGen Consortium.

202/12:15 Interrogating horizontal pleiotropy to infer new causal pathways to disease and explain heterogeneity in Mendelian randomization studies. Y. Cho, P.C. Haycock, T.R. Gaunt, G. Davey Smith, G. Hemani.


Thursday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session E

54. Genetics and Functional Insights into Schizophrenia

Room 6A, Upper Level, San Diego Convention Center

Moderators: Emma Davenport, Broad Inst, Cambridge
  Andy Dahl, UCSF

 

203/11:00 Comparative genetic architectures of schizophrenia in East Asian and European populations. H. Huang, M. Lam, C. Chen, S. Qin, P. Sham, N. Iwata, K.S. Hong, S.G. Schwab, W. Yue, M. Tsuang, J.J. Liu, X. Ma, R.S. Kahn, Y. Shi, Psychiatric Genomics Consortium - East Asia workgroup.

204/11:15 Exome sequencing of 23,851 cases implicates novel risk genes and provides insights into the genetic architecture of schizophrenia. T. Singh, B.M. Neale, M.J. Daly, on behalf of the SCHEMA consortium.

205/11:30 Cell type-specific alternation in schizophrenia and bipolar disorder. R. Dai, L. Chen, S. Liu, Y. Chen, J. Dai, G. Yu, Y. Wang, C. Chen, C. Liu.

206/11:45 Genome-wide characterization of risk genes reveals spatiotemporal heterogeneity of schizophrenia. Y. Ji, Q. Wang, R. Chen, Q. Wei, H. Yang, B. Li.

207/12:00 Differential histone modifications in 250 schizophrenia cases and 330 controls. K. Girdhar, G.E. Hoffman, Y. Jiang, L. Brown, O. Devillers, YC. Wang, H. Shah, E. Zharovsky, R. Jacobov, J. Wiseman, E. Flatow, R. Park, J.S. Johnson, B.S. Kassim, P. Sklar, P. Roussos, S. Akbarian, PsychENCODE Consortium, CommonMind Consortium.

208/12:15 CRISPR-mediated multiplex epigenomic perturbation of functional noncoding sequences of schizophrenia in hiPSC models. S. Zhang, H. Zhang, M. Streit, J. Shi, AR. Sanders, Z. Pang, PV. Gejman, X. He, J. Duan.


Thursday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session E

55. The Contribution of Structural Variation to Neurological Disorders

Room 6B, Upper Level, San Diego Convention Center

Moderators: Clement Chow, Univ Utah, Salt Lake City
  Megan Y. Dennis, UC Davis

 

209/11:00 Local and global chromatin interactions are altered by large genomic deletions associated with human brain development. C. Purmann, X. Zhang, Y. Zhang, X. Zhu, M.S. Haney, T. Ward, J. Yao, S.M. Weissman, A.E. Urban.

210/11:15 Human-specific NOTCH2NL genes affect notch signaling and cortical neurogenesis. F.M.J. Jacobs, G.A. Lodewijk, M. Mooring, C.M. Bosworth, A.D. Ewing, G.L. Mantalas, A.M. Novak, A. van den Bout, A. Bishara, J.L. Rosenkrantz, J. Lorig-Roach, A.R. Field, M. Haeussler, A. Bhaduri, T.J. Nowakowski, A.A. Pollen, M.L. Dougherty, X. Nuttle, M.C. Addor, S. Zwolinski, S. Katzman, A. Kriegstein, E.E. Eichler, S.R. Salama, I. Fiddes, D. Haussler.

211/11:30 Tissue-specific molecular signatures associated with 16p11.2 reciprocal genomic disorder. P. Razaz, S. Erdin, D.J. Tai, T. Aneichyk, T. Arbogast, A. Ragavendran, K. Mohajeri, A. Stortchevoi, B.B. Currall, C.E.F. de Esch, E. Morini, W. Ma, R.J. Kelleher, C. Golzio, N. Katsanis, J.F. Gusella, M.E. Talkowski.

212/11:45 Transcriptome network modeling in cerebral organoids identifies critical cell types in autism-associated copy number variants. E.T. Lim, Y. Chan, G.M. Church.

213/12:00 Functional assessment of Drosophila and Xenopus models shows how 16p12.1 deletion leads to neurodevelopmental defects and is modulated by rare variants in the genetic background. L. Pizzo, M. Lasser, P. Ingraham, D. Mayanglambam, E. Huber, M. Jensen, A. Krishnan, M. Kelly, A. Weiner, M. Rolls, L. Lowery, S. Girirajan.

214/12:15 Detection of copy number variations in epilepsy using exome data. N. Tsuchida, M. Nakashima, M. Kato, Y. Uchiyama, E. Imagawa, T. Mizuguchi, T. Atsushi, N. Miyake, H. Nakajima, H. Saitsu, S. Miyatake, N. Matsumoto.


Thursday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session E

56. Leveraging GWAS Data with Other Data Types

Room 6C, Upper Level, San Diego Convention Center

Moderators: Candace Middlebrooks, NHGRI, Bethesda
  Jacqueline MacArthur, European Bioinformatics Inst, Cambridge, UK

 

This session is not eligible for continuing education credit.

NOTE: Overflow seating for this session is available in Room 2.

 

215/11:00 GWAS and pathway analyses in childhood and adult-onset asthma in UK Biobank identifies novel loci, effector genes and pathways that highlight distinct aetiology between subtypes. K. Song, T. Lee, J. Hoffman, R. Scott, L. Yerges-Armstrong, S. Ghosh.

216/11:15 Integration of GWAS summary statistics and miRNA-target gene network with tissue-specific miRNA expression profile identified novel pathogenesis of complex human traits implicated in tissue specificity. S. Sakaue, K. Yamamoto, Y. Okada.

217/11:30 A fast linkage method for large GWAS cohorts with related individuals. G.J.M. Zajac, S.A. Gagliano, G.R. Abecasis.

218/11:45 Genome wide meta-analysis of parent-of-origin effects of asthma, atopy and airway hyperresponsiveness in four cohorts. A. Eslami, L. Akhabir, J.M. Vonk, A.B. Becker, A.L. Kozyrskyj, A.J. Sandford, G.H. Koppelman, C. Laprise, D. Daley.

219/12:00 Simultaneously modeling host genetics and microbiome composition reveals the heritability and the proportion of variance explained due to the microbiome of immune-related traits. E.R. Davenport, T.D. Spector, R.E. Ley, A.G. Clark.

220/12:15 A little data goes a long way: Finding target genes across the GWAS Catalog by colocalizing GWAS and eQTL top hits. C. Guo, M.R. Nelson, J. Esparza-Gordillo, M.R. Hurle, T. Johnson, K.B. Sieber.


Thursday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session E

57. New Genes, Old Genes, and Novel Functions in the Central Nervous System

Room 6D, Upper Level, San Diego Convention Center

Moderators: Suma Shankar, UC Davis
  Trenell Mosley, Emory Univ Sch Med, Atlanta

 

221/11:00 Understanding the molecular basis of a novel ADPRHL2-mediated neuropathology. S.G. Ghosh, K. Becker, H. Huang, T.D. Salazar, G. Chai, H. Wang, G. Haddad, M. Karakaya, B. Wirth, J.M. van Hagen, N.I. Wolf, R. Maroofian, H. Houlden, S. Cirak, J.G. Gleeson.

222/11:15 Argininosuccinate lyase is required for central regulation of catecholamines synthesis. S. Lerner, R. Eilam, M. Prigge, M. Tsoory, Y. Kuperman, E. Anderzhanova, O. Yizhar, A. Chen, A. Erez.

223/11:30 Genetic and functional approaches highlight a novel ciliary complex implicated in Joubert syndrome. J.C. Van De Weghe, T.D. Rusterholz, B. Latour, A. Gomez, UW Center for Mendelian Genomics, M. Bamshad, D. Nickerson, R. Roepman, R. Bachmann-Gagescu, D. Doherty.

224/11:45 The loss of fragile X mental retardation protein alters the development of human forebrain organoid. Y. Kang, F. Zhang, Y. Li, Z. Wen, P. Jin.

225/12:00 Investigating the role of rare DPP6 missense variants in dementia: Insights from in vitro investigation of protein stability. R. Cacace, B. Heeman, C. Van Broeckhoven.

226/12:15 Genetic variation in the AnkyrinG interactome causes a range of neurological disorders. F. Kooy, I.M. van der Werf, S. Jansen, B.B.A. de Vries, G. Vandeweyer.


Thursday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session E

58. Skin and Bones: Mendelian Skeletal, Connective Tissue, and Ectodermal Phenotypes

Room 6E, Upper Level, San Diego Convention Center

Moderators: Philippe M. Campeau, Univ Montreal, Canada
  Margot A. Cousin, Mayo Clinic, Rochester

 

227/11:00 SLC10A7 mutations in human and mouse cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects. J.M. Dubail, C. Huber, S. Chantepie, S. Sonntag, B. Tüysüz, E. Mihci, C.T. Gordon, E. Steichen-Gersdorf, J. Amiel, B. Nur, I. Stolte-Dijkstra, A.M. van Eerde, K.L. van Gassen, C.C. Breugem, A. Stegmann, C. Lekszas, R. Maroofian, E.G. Karimiani, A. Bruneel, N. Seta, A. Munnich, D. Papy-Garcia, M. De La Dure-Molla, V. Cormier-Daire.

228/11:15 A homozygous missense variant in NUDT6 is responsible for an autosomal recessive form of osteogenesis imperfecta. O. Essawi, S. Symoens, B. Guillemyn, D. Syx, F. Malfait, B. Callewaert, A. Willaert, T. Essawi, P. Coucke.

229/11:30 ­­Mutations in PIK3C2A cause a novel ciliopathy characterized by syndromic short stature associated with cataracts and skeletal abnormalities. D.A. Buchner, D. Tiosano, A. Chen, M. Schueler, M.M. Hitzert, A. Wiesener, A. Berguaz, A. Mory, A. Yuan, F. Gulluni, P. Rump, H. van Meer, D.A. Sival, V. Haucke, K.X. Knaup, A. Reis, N.N. Hauer, E. Hirsch, B.M. McDermott, B.D. Perkins, R. Roepman, R. Pfundt, C.T. Thiel, M.S. Wiesener, M.G. Aslanyan, H.N. Baris.

230/11:45 FAM92A underlies non-syndromic postaxial polydactyly in humans and an abnormal limb and digit skeletal phenotype in mice. S. Leal, I. Schrauwen, A.P.J. Giese, A. Aziz, D.T. Lafont, I. Chakchouk, R.L.P. Santos-Cortez, K. Lee, A. Acharya, U.W. C.M.G., D.A. Nickerson, M.J. Bamshad, G. Ali, S. Riazuddin, M. Ansar, W. Ahmad, Z.M. Ahmed.

231/12:00 Mutations in PERP cause novel forms of recessive and dominant keratoderma with hair abnormalities. L.M. Boyden, J. Zhou, R. Hu, Y.H. Lim, R.P. Lifton, K.A. Choate.

232/12:15 ­­Biallelic loss-of-function variants in the calcium-binding protein encoding gene CCDC47 cause a novel disease characterized by woolly hair, liver dysfunction, pruritus, dysmorphic features, and global developmental delay. M. Morimoto, E. Maguire, Z. Ammous, X. Song, D. Pehlivan, C. Lau, E. Karaca, H. Waller-Evans, C.R. Holst, X. Chepa-Lotrea, E. Macnamara, T. Tos, S. Isikay, M. Nehrebecky, C. Gonzaga-Jauregui, J.D. Overton, K.W. Brigatti, M. Klein, T.C. Markello, J.E. Posey, D.R. Adams, E.G. Puffenberger, K.A. Strauss, E. Lloyd-Evans, J.R. Lupski, W.A. Gahl, M.C.V. Malicdan.


Thursday, October 18

11:00 AM–12:30 PM

Concurrent Platform Session E

59. Genetic Variant Effects on Blood Lipids

Room 6F, Upper Level, San Diego Convention Center

Moderators: Ron Do, Icahn Sch Med Mount Sinai, New York
  Jennifer Below, Vanderbilt Univ Med Ctr, Nashville

 

233/11:00 Meta-analysis of 1.2 million individuals for blood lipid levels. I. Surakka, S.E. Graham, G. Abecasis, G. Peloso, S. Kathiresan, C.J. Willer, Global Lipids Genetics Consortium.

234/11:15 Genome-wide study of statin usage and related adverse events using national drug prescription registries from Estonia and Finland. K. Krebs, P. Helkkula, V. Kukuškina, R. Mägi, S. Ripatti, L. Milani.

235/11:30 Monogenic and polygenic predictors of plasma lipid extremes from whole genome sequencing in diverse ancestries: The NHLBI TOPMed program. G.M. Peloso, NHLBI TOPMed Lipids Working Group.

236/11:45 A missense variant in B4GALT1 reduces low-density lipoprotein and fibrinogen. M. Montasser, A. Howard, R. McFarland, C. Van Hout, G. Della Gatta, B. Shen, N. Li, G. Tzoneva, N. Gosalia, A. Economides, B. Mitchell, M. Healy, J. O'Connell, E. Streeten, N. Zaghloul, C. Sztalryd-Woodle, S. Taylor, A. Shuldiner.

237/12:00 Evaluating the contribution of cell-type specific alternative splicing to variation in lipid levels. K.A.B. Gawronski, W. Bone, E. Pashos, Y. Park, X. Wang, W. Yang, D. Rader, K. Musunuru, B. Voight, C. Brown.

238/12:15 Leveraging functional genomic data for etiologic insight from GWAS summary statistics. C. Quick, G. Abecasis, M. Boehnke, X. Wen, H.M. Kang.


Thursday, October 18

4:15 PM–4:30 PM

60. ASHG William Allan Award Presentation and Lecture: The Genetics of Common Disease: From Variants to Function

Hall C, Ground Level, San Diego Convention Center

The ASHG William Allan Award recognizes a scientist for substantial and far-reaching scientific contributions for human genetics. It was established in 1961 in memory of William Allan, MD (1881-1943), one of the first American physicians to conduct extensive research on human genetics and hereditary diseases.

Introduction: Mark Daly, PhD, Broad Institute of MIT and Harvard

Recipient:
Eric S. Lander
Eric Lander, PhD, Broad Institute of MIT and Harvard

Dr. Lander helped pioneer the use of genome-wide expression analysis to characterize tumors. This initial work led to the creation of The Cancer Genome Atlas (TCGA), a comprehensive catalog of cancer genes that defines and details the molecular architecture of the most common human malignancies. In 2004, Dr. Lander launched the Broad Institute, a research institution in which scientists collaboratively tackle challenges in genomic medicine. He has also done groundbreaking work on human population history, genome evolution, regulatory elements, long non-coding RNAs, three-dimensional folding of the human genome, and genome-wide functional screens to discover the genes essential for biological processes.

 


Thursday, October 18

4:30 PM–4:35 PM

61. C.W. Cotterman Awards Presentation

Hall C, Ground Level, San Diego Convention Center

Each September, the editorial board of The American Journal of Human Genetics selects two articles that best represent outstanding contributions to the field of genetics. The two awards are presented for the best papers published in AJHG during the previous year, on which the first author was either a pre- or postdoctoral trainee and is an ASHG member. The awards will be presented with a monetary award and certificate.

 


Thursday, October 18

4:35 PM–4:45 PM

62. Announcement of the Semi-finalists and Finalists for the Charles J. Epstein Trainee Awards for Excellence in Human Genetics Research

Hall C, Ground Level, San Diego Convention Center

ASHG provides merit-based research awards for trainees (predoctoral and postdoctoral, including genetic counseling trainees) on the basis of submitted, competitive abstracts and on-site presentations at the 2018 Annual Meeting. This year’s semi-finalists and 18 finalists will be acknowledged.

 


Thursday, October 18

4:45 PM–5:00 PM

63. ASHG Arno Motulsky-Barton Childs Award for Excellence in Human Genetics Education Presentation and Lecture: Origin of Our Species (Homo praeceptor)

Hall C, Ground Level, San Diego Convention Center

The ASHG Award for Excellence in Human Genetics Education recognizes those who have made significant contributions of exceptional quality and great importance to human genetics education.

Introduction: Judy Hall, MD, University of British Columbia

Recipient:
Jan M. Friedman
Jan M. Friedman, MD, PhD, University of British Columbia

Dr. Friedman has worked with several organizations that focus on the betterment of the science community. He was the founding president of the Association of Professors of Human or Medical Genetics (APHMG), incorporated in 1995. In 1998, the group successfully led an effort to increase the presence of genetics education in medical schools by specifically outlining the necessary clinical genetics objectives for medical students. Dr. Friedman’s research focuses on clinical applications of genomic technology, birth defects epidemiology and clinical teratology, and clinical studies of neurofibromatosis. He has authored more than 300 papers and trained numerous graduate students, medical students, residents, and fellows.

 


Thursday, October 18

5:00 PM–6:30 PM

64. Presidential Symposium: Origins of Our Species: Advances in Our Understanding of Ancient Humans in Africa

Hall C, Ground Level, San Diego Convention Center

Moderators: Charles N. Rotimi, NHGRI, Bethesda
  Sarah Tishkoff, Univ Pennsylvania, Philadelphia

 

This exciting session is focused on recent advances in our understanding of human origins, migration, and health, with a focus on findings in ancient and modern Africa. The speakers will discuss current understanding of early hominin including anthropological and genetic evidence that points to earlier emergence of modern humans and apparent genetic contributions from prior species. The recognition of this deep and braided history of our species in Africa has consequences for understanding genetic variation in modern human populations and their influence on health and disease. Each speaker will have time for audience Q&A, and the session will end with a moderated panel discussion with the moderators and speakers.

 

5:00 PM   Current status and future directions. J. Hawks. Univ Wisconsin Madison.

5:25 PM   Reconstructing the prehistory of Africa: The narrative of the genes. H. Soodyall. Natl Hlth Lab Service & Univ Witwatersrand, Johannesburg, South Africa.

5:50 PM   Genetic medicine research in Africa: Promise, problems, prospects. A. Wonkam. Univ Cape Town, South Africa.

6:15 PM   Moderated panel discussion.


Friday, October 19

9:00 AM–10:00 AM

Concurrent Platform Session F

65. Mutational Processes in Cancer

Ballroom 20A, Upper Level, San Diego Convention Center

Moderators: Rachel Burnside, LapCorp, Durham
  Rajarshi Ghosh, Baylor Col Med, Houston

 

239/9:00 Genomic, transcriptomic, and clinical determinants associated with aberrant clonal expansions. MJ. Fave, E. Bader, P. Mehanna, V. Bruat, P. Awadalla.

240/9:15 APOBEC3A or APOBEC3B? Causes and consequences of APOBEC mutagenesis in human cancers. R. Banday, O. Onabajo, S. Lin, A. Obajemu, J. Vargas, L. Prokunina-Olsson.

241/9:30 Comprehensive analysis of indels in whole-genome microsatellite regions and microsatellite instability across 21 cancer types. A. Fujimoto, M. Fujita, Y. Shiraishi, K. Maejima, K. Nakano, T. Tsunoda, S. Imoto, S. Miyano, N. Matsubara, N. Tomita, H. Nakagawa.

242/9:45 Mismatch-repair signature mutations activate gene enhancer activity across colorectal cancer epigenomes. S. Hung, A. Saiakhova, Z. Faber, C. Bartels, D. Neu, G. Dhillon, E. Hong, I. Bayles, M. Kalady, S. Markowitz, P. Scacheri.


Friday, October 19

9:00 AM–10:00 AM

Concurrent Platform Session F

66. Genetics of Cancer Therapy Response and Resistance

Ballroom 20BC, Upper Level, San Diego Convention Center

Moderators: Ekta Khurana, Weill Cornell Med Col, New York
  Deborah Ritter, Baylor Col Med, Houston

 

243/9:00 Longitudinal monitoring of AML tumors with high-throughput single-cell DNA sequencing reveals rare clones prognostic for disease progression and therapy response. D.J. Eastburn, C.M. McMahon, A. Viny, R. Bowman, L. Miles, R. Durruthy-Durruthy, R.L. Levine, M. Carroll, C.C. Smith, A.E. Perl.

244/9:15 Genome-wide CRISPR screening and integrative genomic analyses identify novel mechanisms of glucocorticoid resistance in acute lymphoblastic leukemia. R.J. Autry, S.W. Paugh, R.M. McCorkle, R.A. Carter, J. Liu, L. Shi, D.C. Ferguson, C.E. Lau, J.C. Panetta, E.J. Bonten, J.A. Beard, K.R. Crews, W. Yang, J.D. Diedrich, D. Pei, S.E. Karol, C. Smith, K.G. Roberts, S. Pounds, S.M. Kornblau, C.G. Mullighan, J.J. Yang, D. Savic, S. Jeha, C.H. Pui, C. Cheng, J. Yu, C. Gawad, M.V. Relling, W.E. Evans.

245/9:30 High-throughput identification of genes involved in single and multi-drug resistance in pancreatic cancer with pooled CRISPR screening. R.C. Ramaker, A.A. Hardigan, E. Gordon, R.M. Myers, S.J. Cooper.

246/9:45 An integrative functional genomic approach identifies genotype-specific therapeutic vulnerabilities in lung cancer. A.H. Berger, A. Vichas, N. Nkinsi, F. Mundt, F. Piccioni.


Friday, October 19

9:00 AM–10:00 AM

Concurrent Platform Session F

67. Genetic Architecture of Hematopoiesis

Ballroom 20D, Upper Level, San Diego Convention Center

Moderators: Charles Farber, Univ Virginia, Charlottesville
  Alex Reiner, Fred Hutchinson Cancer Res Ctr, Univ Washington, Seattle

 

247/9:00 Deconvolution of CRISPR tiling screen data for the discovery and dissection of functional non-coding elements. J.Y. Hsu, C.P. Fulco, M.A. Cole, M.C. Canver, D. Pellin, F. Sher, R. Farouni, K. Clement, J.A. Guo, L. Biasco, S.H. Orkin, J.M. Engreitz, E.S. Lander, J.K. Joung, D.E. Bauer, L. Pinello.

248/9:15 Interrogation of human hematopoiesis at single-cell and single-variant resolution. J.C. Ulirsch, C.A. Lareau, E.L. Bao, L.S. Ludwig, M.H. Guo, C. Benner, A.T. Satpathy, R. Salem, J.N. Hirschhorn, H.K. Finucane, M.J. Aryee, J.D. Buenrostro, V.G. Sankaran.

249/9:30 Macromap: A systematic map of condition-specific genetic effects on expression in immune response based in induced Pluripotent Stem Cell (iPSC)-derived macrophages. N.I. Panousis, A. Knights, C. Gomez, L. Boquete-Vilarino, A. Tsingene, D. Gaffney.

250/9:45 Blood cell genetic architecture and phenotype prediction. D. Vuckovic, H. Ponstingl, P. Akbari, T. Jiang, W.J. Astle, A.S. Butterworth, M. Inouye, N. Soranzo.


Friday, October 19

9:00 AM–10:00 AM

Concurrent Platform Session F

68. Enhancers and Noncoding Regions

Room 6A, Upper Level, San Diego Convention Center

Moderators: Alon Goren, UCSD
  Rachel Gate, UCSF

 

251/9:00 High throughput characterization of genetic effects on DNA:protein binding and gene transcription. C. Kalita, C. Brown, A. Freiman, X. Wen, F. Luca, R. Pique-Regi.

252/9:15 Identifying novel regulatory elements using RELICS, a statistical framework for the analysis of CRISPR regulatory screens. P.C. Fiaux, H. Chen, I. Luthra, G. McVicker.

253/9:30 Functional interpretation of genetic variants using deep learning predicts impact on epigenome. G.E. Hoffman, P. Roussos.

254/9:45 Disease heritability enrichment of regulatory elements is concentrated in elements with ancient sequence age and conserved function across species. M.L.A. Hujoel, S. Gazal, F. Hormozdiari, B. van de Geijn, A.L. Price.


Friday, October 19

9:00 AM–10:00 AM

Concurrent Platform Session F

69. Using RNA-seq to Improve DNA Sequence Interpretation

Room 6B, Upper Level, San Diego Convention Center

Moderators: Ryan Layer, Univ Colorado, Boulder
  Alex Kotlar, Emory Univ Sch Med, Atlanta

 

255/9:00 Rare disease diagnosis by integrating RNA sequencing in the Undiagnosed Diseases Network. S. Chen, H. Lee, L. Fresard, YC. Lee, A. Eskin, N. Hanchard, N. Stong, M. Wheeler, B. Dawson, D. Murdock, L. Burrage, J. Rosenfeld, V. Shashi, D. Bonner, C. Esteves, D. Goldstein, S. Montgomery, S. Nelson, B. Lee, Undiagnosed Diseases Network Members.

256/9:15 Clinical utility of combining blood-based monocyte assay and RNA sequencing with gene-panel testing: Higher diagnosis of 306 Dysferlinopathy-suspected US patients. S. Chakravorty, S. Shenoy, K. Berger, D. Arafat, B. Nallamilli, L. Rufibach, S. Shira, G. Gibson, M. Hegde.

257/9:30 Integrating whole genome sequencing and RNA sequencing through allele specific expression analysis in the COPDGene study. M.M. Parker, S. Lee, R.P. Chase, D. Qiao, E.K. Silverman, C.P. Hersh, M.H. Cho, P.J. Castaldi, NHLBI TOPMed Investigators, COPDGene Investigators.

258/9:45 OUTRIDER and FraseR: Statistical methods to detect aberrant events in RNA sequencing data. C. Mertes, F. Brechtmann, A. Matusevičiūtė, V.A. Yépez, Z. Avsec, M. Herzog, D.M. Bader, L. Kremer, H. Prokisch, J. Gagneur.


Friday, October 19

9:00 AM–10:00 AM

Concurrent Platform Session F

70. Cell Types, States, and Networks

Room 6C, Upper Level, San Diego Convention Center

Moderators: Tomi Pastinen, Children's Mercy Hosp Kansas City
  Emily Hodges, Vanderbilt Univ, Nashville

 

259/9:00 Biological factors strongly impact cell type abundances in human tissues. M. Oliva, B.E. Stranger, S. Kim-Hellmuth, F. Aguet.

260/9:15 Using multi-tissue gene expression to estimate individual- and cell-type-specific gene expression via deconvolution. J. Wang, B. Devlin, K. Roeder.

261/9:30 Addressing confounding artifacts in reconstruction of gene co-expression networks. P. Parsana, C. Ruberman, A.E. Jafee, M.C. Schatz, A. Battle, J.T. Leek.

262/9:45 Brain region- and developmental time-specific genes are enriched in psychiatric genetics signals. C. Jiao, QT. Meng, KL. Wang, C. Chen, CY. Liu.


Friday, October 19

9:00 AM–10:00 AM

Concurrent Platform Session F

71. Genetic Effects on Pregnancy and Fetal Health

Room 6D, Upper Level, San Diego Convention Center

Moderators: Amy Breman, Indiana Univ Diagnostic Genet & Genomics, Indianapolis
  Martin Breuss, UCSD

 

This session is not eligible for continuing education credit.

NOTE: Overflow seating for this session is available in Room 1AB.

 

263/9:00 Morning sickness and hyperemesis gravidarum: Genetic and functional analysis of placenta and appetite hormone GDF15 supports causality. M.S. Fejzo, P.A. Fasching, M.O. Schneider, J. Schwitulla, M.W. Beckmann, E. Schwenke, D. Arzy, R. Tian, K.W. MacGibbon, P.M. Mullin.

264/9:15 Causative genes and mechanism of androgenetic hydatidiform moles. N.M.P. Nguyen, Z. Ge, R. Reddy, S. Fahiminiya, P. Sauthier, R. Bagga, F. Sahin, S. Mahadevan, M. Osmond, M. Breguet, K. Rahimi, L. Lapensee, K. Hovanes, R. Srinivasan, I. Van den Veyver, T. Sahoo, A. Ao, J. Majewski, T. Taketo, R. Sllim.

265/9:30 Expanded targeted exome sequencing in fetuses with ultrasound abnormalities reveals an important fraction of cases with associated gene defects. C.G. Pangalos, B. Hagnefelt, S. Karapanou, C. Konialis.

266/9:45 Pre-natal inflammation primes the neonatal intestine for endotoxin tolerance. E. Banfield, W. Fulton, I. Burd, C. Sodhi, D. Hackam.


Friday, October 19

9:00 AM–10:00 AM

Concurrent Platform Session F

72. Translating Cardiovascular Genetics to Patient Care

Room 6E, Upper Level, San Diego Convention Center

Moderators: Gina Marie Peloso, Boston Univ
  Jason H. Karnes, Univ Arizona, Tucson

 

267/9:00 Predicting incident cardiometabolic and cancer events using highly polygenic risk scores. N. Mars, J. Koskela, P. Ripatti, T. Kiiskinen, A.S. Havulinna, L. Groop, A. Palotie, M. Daly, V. Salomaa, E. Widén, S. Ripatti.

268/9:15 Genome-wide association meta-analysis identifies 12 common risk alleles for Brugada syndrome, a rare cardiac arrhythmia disorder. R. Redon, J. Barc, R. Tadros, C. Dina, F. Manevy, J.B. Gourraud, Y. Mizusawa, K.E. Odening, C. Antzelevitch, M.P. van den Berg, M.M. Borggrefe, P.D. Lambiase, J. Saenen, E. Schulze-Bahr, T. Robyns, O. Campuzano, E. Arbelo, A. Leenhardt, S.G. Priori, L. Crotti, P. Mabo, C. de Asmundis, D.F. Giachino, E. Behr, M. Haissaguerre, J.R. Gimeno, J.J. Schott, V. Probst, A.A.M. Wilde, C.R. Bezzina, The Rythmogene Working Group, The BrS Genetics Consortium.

269/9:30 High-throughput functional genomics of cardiac sodium channel variants. A.M. Glazer, B.M. Kroncke, K.A. Matreyek, T. Yang, J. Salem, D.M. Fowler, D.M. Roden.

270/9:45 Receiving personal genome-based disease risk information motivates individuals to take action to prevent cardiovascular disease (CVD). E. Widen, J. Aro, P. Pollanen, K. Hotakainen, J. Partanen, S. Ripatti.


Friday, October 19

9:00 AM–10:00 AM

Concurrent Platform Session F

73. Therapeutic Development: Modulating Cellular Effectors

Room 6F, Upper Level, San Diego Convention Center

Moderators: Charles Schwartz, J C Self Research Inst, Greenwood Genet Ctr
  Chiara Manzini, George Washington Univ, Washington, D.C.

 

271/9:00 Mechanistic and therapeutic interrogation of a novel mouse model of vascular Ehlers-Danlos syndrome. G. Rykiel, C.J. Bowen, J.C. Giadrosic, M. Helmers, H.C. Dietz.

272/9:15 Effect of soluble activin receptor type IIB-Fc on hindlimb skeletal muscle contractile and mitochondrial function in the osteogenesis imperfecta model (oim) mouse. Y. Jeong, V. Gremminger, G.M. Meers, R.S. Rector, C.L. Phillips.

273/9:30 Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum: An open-label study in adults and children. L. Faivre, V. Parker, K. Keppler-Noreuil, M. Luu, N. Oden, L. De Silva, J. Sapp, K. Andrews, M. Bardou, K. Chen, T. Darling, B. Goldspiel, S. Hadj-Rabia, J. Harris, G. Kounidas, P. Kumar, M. Lindhurst, R. Loffroy, L. Martin, A. Phan, K. Röther, B. Widemann, P. Wolters, C. Coubes, L. Pinson, M. Willems, C. Vincent-Delorme, P. Vabres, R. Semple, L. Biesecker.

274/9:45 The combinative effect of testosterone treatment and the timing of diagnosis on neurocognitive abilities and ADHD in 47,XXY (Klinefelter Syndrome). C. Samango-Sprouse, P. Lasutschinkow, S. Chea, T. Sadeghin, A. Gropman.


Friday, October 19

10:30 AM–12:30 PM

Concurrent Invited Session II

74. Advances in Unraveling the Genetic, Molecular, and Clinical Complexity of Autism

Ballroom 20A, Upper Level, San Diego Convention Center

Moderators: Maria Chahrour, Univ Texas Southwestern Med Ctr, Dallas
  Brian O'Roak, Oregon Hlth & Sci Univ, Portland

 

Autism spectrum disorder (ASD) is a constellation of neurodevelopmental presentations with genetic and non-genetic causes. Next-generation sequencing technologies have allowed for recent strides in the genetics of ASD, while the molecular mechanisms underlying disease pathogenesis have remained elusive, hindering therapy development. Our goal for this invited session is to provide an overview of current areas of emphasis in ASD research spanning genomics and genetics, molecular pathways, sex-specific signaling, and phenotyping strategies to guide drug development. Importantly, as gene discovery and functional studies continue, new parallels are discovered between ASD and other neuropsychiatric, neurodegenerative, and complex disorders, which can be leveraged to understand pathogenesis and develop therapies. We will start with human genetics of ASD and how next-generation sequencing has changed the way we think of the disorder, also focusing on how to determine whether a candidate gene mutation can be reliably considered as causative. We will then discuss how protein degradation has been involved as a mechanism for ASD and how it is linked to alterations in circuit function and cognitive/social behavior. We will explore how we can use mouse lines recapitulating human mutations to study the striking 4:1 male:female bias in ASD. Finally, we will conclude with patient phenotyping of the genetic subtypes in ASD, and efforts to leverage all these molecular findings to develop therapies for neurodevelopmental disorders. Overall, we strive to spur discussion across different fields and demonstrate that better understanding of a disorder as complex as ASD can be deepened by a multidisciplinary approach.

 

10:30 AM   Unlocking autism's genetic etiology: Lessons learned from new mutations. B. O'Roak. Oregon Hlth & Sci Univ, Portland.

11:00 AM   Rare inherited mutations in autism spectrum disorder. M. Chahrour. Univ Texas Southwestern Med Ctr, Dallas.

11:30 AM   Sex-specific intracellular signaling as a cause for male bias in autism. M. Manzini. George Washington Univ, Washington.

12:00 PM   Prospective phenotyping of ASD using a genotype-first approach. R. Bernier. Univ Washington, Seattle.


Friday, October 19

10:30 AM–12:30 PM

Concurrent Invited Session II

75. Clinical Spotlight: ASHG/ESHG Building Bridges: Prenatal Genetic Testing: Recent Advances and Current Challenges

Room 6C, Upper Level, San Diego Convention Center

Moderators: Heather Mefford, ASHG 2018 Program Committee Chair
  Joris Veltman, ESHG 2018 Program Chair

 

In recent years, prenatal genetic testing has made great advances in predicting birth defects and genetic disorders while bringing unexpected challenges. Experts from ASHG and ESHG will present issues that have arisen as genetic tests become more common, from implementing newer techniques like non-invasive prenatal testing (NIPT) to handling return of maternal incidental findings. The session will close with a dynamic panel discussion, where the speakers will compare and contrast solutions to current challenges in the American and European healthcare systems.

ESHG logo
ASHG logo

 

10:30 AM   Implementing NIPT as part of a national prenatal screening program: The Dutch TRIDENT studies. E. Sistermans. VU Univ Med Ctr, Amsterdam, Netherlands.

10:50 AM   Double trouble: Incidental findings on mother and fetus as a result of noninvasive prenatal testing for aneuploidy. D. Bianchi. NIH, Bethesda.

11:10 AM   Invasive and non-invasive prenatal diagnosis for monogenic disorders: Where are we in the U.S.? I. Van den Veyver. Baylor Col Med, Houston.

11:30 AM   Transforming prenatal diagnosis of monogenic disorders in the UK National Health Service. L. Chitty. UCL Great Ormond St Inst Child Hlth, London, UK.

11:50 AM   Panel discussion: Clinical lab concerns.


Friday, October 19

10:30 AM–12:30 PM

Concurrent Invited Session II

76. Duty to Recontact: Do We Need to Reconsider?

Room 6D, Upper Level, San Diego Convention Center

Moderators: Yvonne Bombard, Univ Toronto, Canada
  James O’Leary, Genet Alliance, Washington

 

NOTE: Overflow seating for this session is available in Room 1AB.

The "duty to recontact" refers to the ‘possible ethical and/or legal obligation of genetics service providers (GSPs) to re-contact former [or current] patients about advances in research that might be relevant to them’ (Fitzpatrick et al, AJHG 1999). While opinions were mixed in a 1999 survey of ASHG members about the existence of such a duty, most respondents felt that recontact was ethically desirable but not feasible. Since then, advances in sequencing technologies and genomic information offer improved diagnostic sensitivity, new evidence for clinical relevance of genetic findings, and new interpretations of previously identified genetic variants. Simultaneously, IT solutions are facilitating storage of information and its dissemination to stakeholders (e.g., labs, ordering providers, patients, caregivers, third party payers, researchers, additional or newly treating providers). Some argue that these advances in technology and knowledge support the emergence of an obligation for clinicians, researchers and/or laboratories to recontact patients and research participants when additional information becomes available. This session will review the emerging evidence and stakeholder opinions on recontacting and will present newly developed and/or proposed policy statements of the American Society of Human Genetics, the European Society of Human Genetics and the American College of Medical Genetics & Genomics regarding recontact in the clinical and research arenas, highlighting areas of concordance and discordance across Societies, between the U.S. and Europe, and among the varied contexts. The final 60 minutes of the session will be devoted to discussion and debate, including audience polling and questions from the audience.

 

10:30 AM   Recontacting in clinical genetics: European survey results and ESHG recommendations. F. Forzano. Guy's Hosp, London, United Kingdom.

10:50 AM   Patient recontact for revised clinical genomic results: The ACMG approach. K. L. David. NY Presbyterian Brooklyn Methodist Hosp.

11:10 AM   Duty to recontact in the research environment: The ASHG draft position statement. H. P. Levy. Johns Hopkins Univ, Lutherville.

11:30 AM   Panel discussion and audience feedback.


Friday, October 19

10:30 AM–12:30 PM

Concurrent Invited Session II

77. Exploring the Medical Phenome: The New Frontier of Genetic Discovery

Ballroom 20D, Upper Level, San Diego Convention Center

Moderators: Christopher DeBoever, Stanford Univ
  Gillian Belbin, Mount Sinai Sch Med, New York

 

The implementation of population-scale biobanking combined with Electronic Health Records (EHR) has resulted in the rapid generation of genomic data linked to high-dimensional phenotype data for hundreds of thousands of participants. Often termed the "medical phenome," these data include ICD-CM billing codes, laboratory tests, radiologic reports, prescriptions, and progress notes that span decades of a patient’s life-course. These resources offer a variety of novel opportunities for genetics researchers, including the investigation of the continuum between Mendelian and complex disease, the relative contributions of genetics and environment to disease, the exploration of population genomic health, and the ability to interrogate disease mechanisms. Crucially, these data provide a means to explore the integration of genomic data into clinical practice, allowing researchers to define new models for translational research. To ensure that the genomics community is primed to take full advantage of the medical phenome, new paradigms are required for both formulating questions and implementing research in these large resources. This session brings together four researchers at the cutting edge of developing and applying methods to explore the medical phenome derived from diverse population-scale biobanks. The speakers will describe the challenges and opportunities that arise from high-dimensional phenotypes derived from heterogeneous sources and the non-traditional ascertainment of participants within biobanks. They will present new models and approaches tailored to studying the genetics of disease using the medical phenome and highlight examples of the real-world translational impact of their research.

This session is not eligible for continuing education credit.

 

10:30 AM   Using Nordic health record data in complex diseases genetics. A. Palotie. Broad Inst, Inst for Molec Med Finland, Boston.

11:00 AM   Exploring genome-phenome relationships in ancestrally diverse patient populations. G. Belbin. Mount Sinai Sch Med, New York.

11:30 AM   Empowering disease research in high-dimensional datasets using multivariate models. C. DeBoever. Stanford Univ.

12:00 PM   Skating to where the puck is going to be: Using genetics in medicine after the cost has already been justified. N. J. Cox. Vanderbilt Univ, Nashville.


Friday, October 19

10:30 AM–12:30 PM

Concurrent Invited Session II

78. Impact of Natural Selection on the Genetic Architecture of Complex Traits

Ballroom 20BC, Upper Level, San Diego Convention Center

Moderators: Shamil Sunyaev, Harvard Med Sch & Brigham & Women’s Hosp, Boston
  Laura Hayward, Columbia Univ, New York

 

Evolution and maintenance of complex traits under natural selection has been a long-standing area of genetic research. Polygenic adaptation, stabilizing selection, and negative selection on new mutations can substantially impact the genetic architecture of diseases and complex traits, via direct selection on traits that are correlated with fitness and/or via pleiotropic selection. New methods are being developed to detect the action of natural selection at different time scales, including selection in contemporary humans. This session will discuss recent work on methods that analyze data from large cohorts to detect natural selection and evaluate its impact on diseases and complex traits. The application of these methods has substantially improved our understanding of polygenic disease and complex trait architectures, informing efforts to identify and interpret genetic variation affecting diseases and complex traits.

 

10:30 AM   Polygenic architecture and adaptation of human complex traits. J. Pritchard. Howard Hughes Med Inst, Stanford.

11:00 AM   Detection and quantification of the effect of selection and adaptation on complex traits. P. Visscher. Univ Queensland, Brisbane, Australia.

11:30 AM   Observing natural selection in contemporary humans. M. Ilardo. Univ Utah & UC Berkeley.

12:00 PM   Impact of negative selection on common variant disease architectures. A. Price. Harvard TH Chan Sch Publ Hlth, Boston.


Friday, October 19

10:30 AM–12:30 PM

Concurrent Invited Session II

79. Innovative Strategies to Support the Education of Health Care Providers in Genomic Medicine

Room 6E, Upper Level, San Diego Convention Center

Moderators: Sylvia A. Metcalfe, Murdoch Children's Res Inst, Melbourne, Australia
  Michael Dougherty, Univ Colorado Sch Med, Aurora

 

Educating health professionals about genetics has been a longstanding interest within the genetics professional community. For successful implementation of genomic medicine into health care, new strategies will be needed both for education and system change. This session will highlight what is known about the educational needs of health care providers in genomic medicine, various successful and emerging educational and implementation strategies and evaluation frameworks. All specialists in genomic medicine will play an important role in preparing their non-specialist colleagues for this transformation in clinical care. This session will discuss what’s needed, what works, how to evaluate it and how to implement it.

 

10:30 AM   What is needed and wanted by health care providers to enable integration of genomic medicine into practice? J. C. Carroll. Mount Sinai Hosp, Sinai Hlth Syst Univ Toronto, Canada.

11:00 AM   What works: What are best practices in developing and implementing continuing education programs in genomic medicine for health care providers? K. Reed. Jackson Lab, Farmington.

11:30 AM   What’s new in educating health care professionals in genomic medicine. M. Bishop. Hlth Educ England, Birmingham, United Kingdom.

12:00 PM   How do know your genomics educational intervention for health care providers is effective? A. Nisselle. Murdoch Children’s Res Inst, Melbourne, Australia.


Friday, October 19

10:30 AM–12:30 PM

Concurrent Invited Session II

80. Novel Insights in Aging: Examining the Interface Between Genetics and the Environment

Room 6A, Upper Level, San Diego Convention Center

Moderators: Burcu Darst, Univ Southern California, Los Angeles
  Douglas Dluzen, Morgan State Univ, Baltimore

 

Chronological age is a major risk factor for many chronic diseases, including cancer. Numerous physiological changes occur with age; however, the underlying genetic and environmental factors that contribute to the dysregulation of normal cell and tissue function have not been completely elucidated—in particular, the interaction and influence of the environment on our genetic predispositions to aging. In this session, each speaker will discuss findings from key areas of aging research, including how epigenetic biomarkers of aging may help to explain paradoxical trends in health outcomes, insights into mitochondrial metabolic checkpoint regulation in hematopoietic stem cells in aging and disease, how genetic factors have been shown to influence lifespan in long-lived individuals, and what extreme environments such as space can teach us about human biology and aging. Identifying genetic factors that underlie how humans age, as well as understanding epigenetic changes that occur in normal aging and disease, may one day lead to the development of therapies to improve human health and longevity.

 

10:30 AM   Epigenetic clock analysis of the Hispanic paradox and lifestyle factors. S. Horvath. UCLA.

11:00 AM   Mitochondrial metabolic checkpoint, stem cell aging, and rejuvenation. D. Chen. UC Berkeley.

11:30 AM   What super-seniors can tell us about healthy aging. A. Brooks-Wilson. BC Cancer Agency & Simon Fraser Univ, Vancouver, Canada.

12:00 PM   Epigenetic age and epiallele shifts in cancer, forensics, and astronauts. C. Mason. Weill Cornell Med Col, New York.


Friday, October 19

10:30 AM–12:30 PM

Concurrent Invited Session II

81. The Genetics of Human Proteomes

Room 6B, Upper Level, San Diego Convention Center

Moderators: Hua Tang, Stanford Univ
  Weiping Ma, Icahn Sch Med at Mount Sinai, New York

 

Recent advances in proteomics technologies have enabled characterization of protein expression at unprecedented throughput, accuracy and resolution. This session showcases the tremendous opportunities that quantitative proteomics have afforded for elucidating gene function, post-transcriptional regulation and the genetic basis of diseases. Ruedi Aebersold, a pioneer and leader in quantitative proteomics, will introduce the topic, illustrating how steady-state and dynamic changes of the proteome can be quantified and leveraged to reveal the mechanistic link between genetic variation and phenotypic outcomes. Examples from recent and ongoing studies will illustrate situations in which protein expression captures aspects of gene regulation that are not captured by transcriptomic profiling. Next, Emma Lundberg will describe the latest innovation in delineating proteome variation at a single cell level, as well as the success in resolving the spatial distribution of proteins at a subcellular level. The third talk, by Michael Snyder, will focus on the systematic characterization of proteomic variation in more than twenty human tissues, and the map of genetic variants that affects tissue-specific protein abundance (pQTL). The final speaker, Karin Rodland, will emphasize the translational applications of proteomics, specifically in cancer. She will describe a new approach for identifying therapeutic targets by integrating genomic data with protein abundance and post-translation modification. Together, this session aims to highlight the broad utilities of proteomics in human genetics and medical genetics.

 

10:30 AM   Quantitative proteotype: Linking genetic variation and complex phenotypes. R. Aebersold. ETH Zürich & Univ Zürich, Switzerland.

11:00 AM   Single cell variations of the human proteome. E. Lundberg. KTH Royal Inst Technol, Stanford.

11:30 AM   Genetic basis of protein variation across human tissues. M. Snyder. Stanford Univ.

12:00 PM   Clinical insights from phosphoproteomic and proteogenomic analysis of pathways in cancer. K. Rodland. Pacific Northwest Natl Lab; Oregon Hlth & Sci Univ, Richland.


Friday, October 19

10:30 AM–12:30 PM

Concurrent Invited Session II

82. What's Sex Got to Do with It: Sexual Dimorphism in Human Disease

Room 6F, Upper Level, San Diego Convention Center

Moderators: Chris Cotsapas, Yale Sch Med, New Haven
  Cecilia Lindgren, Oxford Univ, United Kingdom

 

NOTE: Overflow seating for this session is available in Room 7B.

Biological sex is the strongest predictor for a broad array of human traits, but we do not yet understand the mechanisms driving such differences. Height, body composition and metabolic status all vary between the sexes, as does disease incidence, from 90% female in systemic lupus erythematosus and anorexia to 75% male in ankylosing spondylitis and the autism spectrum disorders. These traits are highly heritable, but the majority of the heritability resides on the autosomes, with little evidence for an outsized role of the sex chromosomes in risk. Emerging evidence suggests that autosomal risk variants may have different effects in men and women, indicating a subtler source for dimorphism than sex chromosome variation alone: for example, approximately 50% of loci influencing waist-hip ratio have stronger effects in women than men, with no equivalent and opposite effect in the remainder. In this session, we will explore emerging ideas on the sources of sex differences and how these can lead to mechanistic understanding of the single largest risk factor for human disease.

 

10:30 AM   Sexual dimorphism in autoimmune and inflammatory disease. C. Cotsapas. Yale Sch Med, New Haven.

11:00 AM   Dissecting sexual dimorphism in obesity. C. Lindgren. Oxford Univ, United Kingdom.

11:30 AM   Characterizing genetic correlation across the sexes in UK Biobank. B. M. Neale. Massachusetts Gen Hosp, Boston.

12:00 PM   Sex differences at the molecular level: Lessons from the transcriptome. B. Stranger. Univ Chicago.


Friday, October 19

12:45 PM–1:45 PM

83. ASHG Membership Forum: Charting Our Future

Room 8, Upper Level, San Diego Convention Center

This is an opportunity to interact with ASHG Board members and provide your input and thoughts about the future directions of the Society. Board members will report on key Society business and activities, including preliminary results from ASHG’s recent membership survey.

 


Friday, October 19

4:15 PM–4:30 PM

84. ASHG Mentorship Award Presentation and Lecture: Me + You = Mentorship

Hall C, Ground Level, San Diego Convention Center

The ASHG Mentorship Award recognizes ASHG members who have shown a sustained pattern of exemplary mentorship at the graduate student, postdoctoral, residency, or fellowship level.

Introduction: Sara Pulit, PhD, University Medical Center Utrecht, The Netherlands

Recipient:
Cecilia Lindgren
Cecilia Lindgren, PhD, Big Data Institute, Oxford

Dr. Lindgren began her mentoring while completing her PhD in 1999, by supervising rotation projects at Lund University. Currently, as a Professor at the Big Data Institute at Oxford, she continues supervising students who are completing their PhD and postdoc programs. She has also participated in numerous speaking, lecturing, and tutoring engagements at multiple institutions, furthering her commitment to the education of early-career scientists.

 


Friday, October 19

4:30 PM–4:45 PM

85. ASHG Advocacy Award Presentation and Lecture: Some Thoughts on Advocacy for the 21st Century Human Geneticist

Hall C, Ground Level, San Diego Convention Center

The ASHG Advocacy Award recognizes individuals or groups who have exhibited excellence and achievement in applications of human genetics for the common good.

Introduction: Gail Jarvik, University of Washington

Recipient:
Mary-Claire King
Mary-Claire King, PhD, University of Washington

Best known for her pivotal discoveries in breast cancer genetics, Dr. King has also spent many years as a tireless advocate for the use of genetics to help people and families around the world. Since 1983, Dr. King’s lab at the University of Washington has partnered with the Grandmothers of the Plaza de Mayo in Argentina to reunite families using genetics. In the 1990s, she worked with the United Nations Forensic Anthropology Team, using mtDNA sequencing to identify the remains of victims of extra-judicial execution, and of soldiers who went missing from Vietnam, Cambodia, Korea, and during World War II. Dr. King’s research focuses on the genetic bases of breast and ovarian cancer, schizophrenia, and inherited hearing loss. In 1990, she showed that breast cancer is genetically inherited in some families, and identified the gene BRCA1. Since then, her lab has identified more than 50 genes responsible for a wide range of conditions.

 


Friday, October 19

4:45 PM–5:00 PM

86. ASHG Early-Career Award Presentation and Lecture: New Uses for an Old Enzyme in Single-Cell Omics

Hall C, Ground Level, San Diego Convention Center

The ASHG Early Career Award recognizes the contributions of genetics and genomics scientists in their first 10 years as an independent investigator.

Introduction: Jay Shendure, MD, PhD, University of Washington

Recipient:
Andrew Adey
Andrew Adey, PhD, Oregon Health & Science University

Dr. Adey’s research focuses on the next technical frontier of genomic and epigenetic profiling at a massive scale. Immediately after completing his PhD in Molecular & Cellular Biology, Dr. Adey joined the faculty at OHSU to form his independent research group. Along with his team, he established novel single-cell technologies, including methods to profile thousands of single-cell genomes and epigenomes rapidly and cheaply. This single-cell platform is useful in showing epigenomic changes that enable early cancer progression or that influence response to therapeutic intervention in advanced cancers. His methods are already being used worldwide to better understand the epigenetics of development in both healthy controls and disease models.

 


Friday, October 19

5:00 PM–6:20 PM

87. Featured Plenary Abstract Session II

Hall C, Ground Level, San Diego Convention Center

Moderators: David Wheeler, ASHG 2018 Program Committee
  Christa L. Martin, ASHG 2018 Program Committee

 

Featured Plenary Abstract Sessions include a diverse set of presentations selected from the top-rated abstracts across all topics.

 

275/5:00 Discovery of over 50 novel dominant developmental disorders from exome sequencing of 22,518 parent-child trios. K.E. Samocha, M.E. Hurles, J. Kaplanis, Z. Zhang, S.H. Lelieveld, G. Gallone, H.G. Brunner, C. Gilissen, K. Retterer, on behalf of the Deciphering Developmental Disorders study.

276/5:20 Human 5′ UTR design and variant effect prediction from a massively parallel translation assay. B. Wang, P. Sample, D. Reid, V. Presnyak, I. McFadyen, D. Morris, G. Seelig.

277/5:40 Biallelic variants in TONSL cause SPONASTRIME dysplasia and an expanded spectrum of skeletal dysplasia phenotypes. L. Burrage, J.J. Reynolds, N.V. Baratang, J. Phillips, J. Wegner, A. Christiansen, M.R. Higgs, C. Logan, D. Chitayat, I. Chinn, D. Muzny, R. Gibbs, W. Bi, J.A. Rosenfeld, J. Postlethwait, M. Westerfield, M. Dickinson, J. Orange, M. Adeli, D. Cohn, D. Krakow, A. Jackson, M. Lees, A.C. Offiah, C. Carlston, J.C. Carey, G. Stewart, C.A. Bacino, P.M. Campeau, B.H. Lee, Members of the Undiagnosed Diseases Network.

278/6:00 Large genome-wide analysis of sexual orientation identifies for the first time variants associated with non-heterosexual behavior and reveals overlap with heterosexual reproductive traits. A. Ganna, K.J.H. Verweij, F.R. Day, M.G. Nivard, R. Maier, R. Wedow, A.S. Busch, A. Abdellaoui, S. Guo, F. Sathirapongsasuti, P. Lichtenstein, H. Larsson, S. Lundström, N. Långström, D.A. Hinds, G.W.. Beecham, E.R. Martin, A.R. Sanders, B.M. Neale, J.R.B. Perry, B.P. Zietsch, 23andMe Research Team.


Friday, October 19

6:20 PM–7:20 PM

88. Late-breaking Abstract Session

Hall C, Ground Level, San Diego Convention Center

Moderators: Heather Mefford, ASHG 2018 Program Chair
  Michael Hoffman, ASHG 2018 Program Committee

 

The Late-breaking Abstract Session is a special plenary session developed by the Program Committee to highlight the most exciting research completed after the June abstract deadline.

 

3568/6:20 An atlas of polygenic risk score associations to uncover putative causal relationships across the human phenome. S. Harrison, T.G. Richardson, G. Davey Smith.

3569/6:40 Re-identification of genomic datasets using long-range familial searches. Y. Erlich, T. Shor, I. Pe'er, S. Carmi.

3570/7:00 Patient-customized oligonucleotide therapy for an ultra-rare genetic disease. T.W. Yu, C. Hu, J. Kim, A. Larson, A. Lee, L. Black, C.M. El Achkar, A. Soucy, J. Vaze, M. Armant, N.R. Belur, A. Kuniholm, J. Douville, E. Augustine, M. Pendergast, S. Goldkind, K. Tyndall, B. Goodlett, S. Waisbren, B. Riley, L. Cornelissen, L. Pereira, C. Reed, R. Snyder, A. Patterson, A. Poduri, J. Mazzulli, A. Biffi, O. Bodamer, C. Berde.


Saturday, October 20

8:30 AM–9:30 AM

Concurrent Platform Session G

89. Transcriptome Alterations in Cancer

Ballroom 20A, Upper Level, San Diego Convention Center

Moderators: Renata Pellegrino, Children's Hosp Philadelphia
  Bin Guan, NEI/NIH, Rockville

 

279/8:30 Integrative analysis of diverse transcriptomic alterations to identify cancer-relevant genes across 27 histotypes. N.R. Davidson, D. Demircioglu, N.A. Fonesca, A. Kahles, K.V. Lehmann, F. Liu, L. Urban, J. Goke, R.F. Schwarz, A. Brooks, G. Rätsch, Z. Zhang, A. Brazma, PanCancer Analysis of Whole Genomes and Transcriptomes Working Group (PCAWG-3), PCAWG Consortium.

280/8:45 Transcriptome sequencing illuminates the extent of alternative splicing in multiple myeloma in regards to SF3B1 mutations and identifies a potential MM specific splicing pattern. M.A. Bauer, C. Ashby, R.G. Tytarenko, C.P. Wardell, P. Patel, S. Deshpande, F. van Rhee, M. Zangari, S. Thanendrarajan, C.D. Shinke, F.E. Davies, G.J. Morgan, B.A. Walker.

281/9:00 Cancer eQTL profiles can be recovered from bulk tumor gene expression data by modeling tumor purity. P. Geeleher, .F Wang, Z. Zhang, R.L. Grossman, C. Seoighe, R.S. Huang.

282/9:15 Mapping tumor-immunity-specific expression QTL (tis-eQTL) in cancer. X. Wang, B.L. Fridley, X. Yu, Y.A. Chen, B. Li, C.H. Chung, S. Antonia, J.R. Conejo-Garcia.


Saturday, October 20

8:30 AM–9:30 AM

Concurrent Platform Session G

90. The Non-coding Genome and Disease

Ballroom 20BC, Upper Level, San Diego Convention Center

Moderators: Nicole Soranzo, Wellcome Sanger Inst, Hinxton, UK
  Justin Cotney, UConn Hlth, Farmington

 

283/8:30 Germline GATA3 variants influence chromatin topology and pathogenesis of acute 2 lymphoblastic leukemia. H. Yang, H. Zhang, T. Liu, K. Roberts, M. Qian, Z. Zhang, W. Yang, V. Perez-Andreu, Y. Luan, J. Xu, S. Iyyanki, D. Kuang, H. Xu, S. Reshmi, J. Gastier-Foster, C. Smith, C. Pui, W. Evans, S. Hunger, M. Relling, C. Mullighan, M. Loh, F. Yue, J. Yang.

284/8:45 Using allelic expression to extending rare disease diagnosis beyond coding mutations. P. Mohammadi, S.E. Castel, B. Cummings, D. MacArthur, T. Lappalainen.

285/9:00 Systematic characterization of genetic variants associated with type 1 diabetes for differential binding of 530 transcription factors. P. Benaglio, J. Yan, J. Chiou, N. Nariai, M. Sander, B. Ren, K. Gaulton, K. Frazer.

286/9:15 A novel type 1 diabetes susceptibility locus affects CFTR regulation in pancreatic ductal cells. J. Chiou, R. Geusz, M. Okino, S. Huang, M. Sander, K. Gaulton.


Saturday, October 20

8:30 AM–9:30 AM

Concurrent Platform Session G

91. Biases of Polygenic Risk Scores

Ballroom 20D, Upper Level, San Diego Convention Center

Moderators: Catherine Robertson, Univ Virginia, Charlottesville
  Sarah Gagliano, Univ Michigan, Ann Arbor

 

287/8:30 Evaluating geographic differences in polygenic risk in Finland. S. Kerminen, J. Koskela, A.S. Havulinna, I. Surakka, A.R. Martin, A. Palotie, M. Perola, V. Salomaa, M.J. Daly, S. Ripatti, M. Pirinen.

288/8:45 Polygenic adaptation signals for height are confounded by population structure. R. Maier, M. Sohail, A. Ganna, A. Bloemendal, A. Martin, M. Daly, N. Patterson, B. Neale, I. Mathieson, D. Reich, S. Sunyaev.

289/9:00 Polygenic risk scores perform poorly across populations. B.D. Bitarello, I. Mathieson.

290/9:15 Polygenic risk prediction for the world: A powerful approach for multi-ancestry meta-analysis across globally diverse populations. A.R. Martin, P. Turley, R.K. Walters, H. Li, C.E. Carey, M. Kanai, H. Huang, C.Y. Chen, M. Lam, D. Palmer, M. Zacher, J. Koskela, G. Wojcik, M. Akiyama, C.R. Gignoux, E.E. Kenny, Y. Okada, Y. Kamatani, D. Cesarini, D. Benjamin, S. Ripatti, A. Palotie, B.M. Neale, M.J. Daly.


Saturday, October 20

8:30 AM–9:30 AM

Concurrent Platform Session G

92. Potential Genetic and Epigenetic Therapies of Disease

Room 6A, Upper Level, San Diego Convention Center

Moderators: Bing Yao, Emory Univ, Atlanta
  Torsten Klengel, Harvard Univ, Cambridge

 

291/8:30 Deletion of expanded CGG repeats lowers Fmr1 mRNA and increases FMRP levels in Fmr1 knock-in mice. C.M. Yrigollen, L. Ohl, E. Lim, S. Zheng, K. Brida, Y. Chen, A. Mas Monteys, B.L. Davidson.

292/8:45 Deletion of Hdac9 protein coding exons that also function as transcriptional enhancers, leads to Twist1 haploinsufficiency and results in limb and craniofacial phenotypes. R.Y. Birnbaum, N. Hirsch, F. Shemuluvich, T. Kaplan, D. G. Lupiáñez.

293/9:00 Downregulation of SNCA expression by targeted editing of DNA-methylation: A potential strategy for precision therapy in PD. B. Kantor, L. Tagliafierro, J. Gu, M. Zamora, E. Ilich, C. Grenier, Z. Huang, S. Murphy, O. Chiba-Falek.

294/9:15 Therapeutic modulation of epigenetic memory at a novel TGFβ2 enhancer in systemic sclerosis. J.Y. Shin, J. Beckett, A. Shah, Z. McMahan, J. Paik, M. Sampedro, E. MacFarlane, M.A. Beer, D. Warren, F. Wigley, H.C. Dietz.


Saturday, October 20

8:30 AM–9:30 AM

Concurrent Platform Session G

93. Investigating 3D Genome Structure

Room 6B, Upper Level, San Diego Convention Center

Moderators: Ann Harris, Case Western Reserve Univ Med Sch, Cleveland
  Ian Bayles, Case Western Reserve Univ, Cleveland

 

295/8:30 Reorganization of 3D genome structure may contribute to gene regulatory evolution in primates. I.E. Eres, K. Luo, Y. Gilad.

296/8:45 3D GNOME 2.0: Three-dimensional GeNOme modeling engine of human genome structure at the population scale. D. Plewczynski, M. Wlasnowolski, M. Sadowski, P. Szalaj, A. Kraft, Z. Tang, P. Michalski, Y. Ruan.

297/9:00 Using multiplex non-coding CRISPR deletion libraries to individually perturb CTCF binding sites in the human genome. S.K. Reilly, J. Xue, R. Tewhey, M. Bauer, P.C. Sabeti.

298/9:15 Structural variation and its impact on 3D genome structure in cancer cells. J. Xu, J.R. Dixon, V. Dileep, Y. Zhan, F. Song, V.T. Le, G. G. Yardimci, A. Charkraborty, D.V. Bann, J.R. Broach, R. Kual, L. Zhang, T. Sasaki, J.C. Rivera-Mulia, H. Ozadam, B.R. Lajoie, J.A. Stamatoyannopoulos, S. Hadjur, D. Pezic, C. Ernst, D.T. Odom, R.C. Hardison, F. Ay, W.S. Noble, J. Dekker, D.M. Gilbert, F. Yue.


Saturday, October 20

8:30 AM–9:30 AM

Concurrent Platform Session G

94. Importance of Isoform Expression in Variant Interpretation

Room 6C, Upper Level, San Diego Convention Center

Moderators: David Knowles, Stanford Univ
  Kjong-Van Lehmann, EHT-Zurich, Switzerland

 

299/8:30 Pitfalls of clinical exome and gene-panel testing: Alternative transcripts. D. Bodian, P. Kothiyal, J. Schreiber, T. Vilboux, N. Hauser.

300/8:45 Curating clinically relevant transcripts for the interpretation of sequence variants. M.T. DiStefano, S.E. Hemphill, B.J. Cushman, M.J. Bowser, E. Hynes, A.R. Grant, R.K. Siegert, A.M. Oza, M.A. Gonzalez, S.A. Amr, H.L. Rehm, A.N. Abou Tayoun.

301/9:00 Transcript expression-aware annotation increases power for rare variant discovery in Mendelian and complex disease. B.B. Cummings, K.J. Karczewski, J.A. Kosmicki, F.K. Satterstrom, T. Poterba, F. Aguet, C. Seed, M.J. Daly, D.G. MacArthur.

302/9:15 Converging on transcript annotation from Ensembl/GENCODE and RefSeq. J.E. Loveland, S. Pujar, A. Astashyn, R. Bennett, C. Davidson, O. Ermolaeva, C. Farrell, L. Gil, M. Kay, K. McGarvey, A. McMahon, J. Morales, S. Rangwala, G. Threadgold, F. Cunningham, A. Frankish, T. Murphy.


Saturday, October 20

8:30 AM–9:30 AM

Concurrent Platform Session G

95. Cancer Genomic Testing: Uncertainty and Decision Making

Room 6D, Upper Level, San Diego Convention Center

Moderators: Kunal Sanghavi, Jackson Lab Genomic Med, Farmington
  Peter Levonian, Stanford Hlth Care

 

303/8:30 Patient reported strategies for managing uncertainty related to variants of uncertain significance. S. Makhnoon, B. Shirts, H. Meischke, D. Bowen.

304/8:45 Barriers to cascade testing: Impact on accessibility of a no-additional cost family genetic testing program for hereditary cancer risk. E. Esplin, R. Miller, R. Truty.

305/9:00 Are we ready for genetic testing in all women with breast cancer? P. Salyer, M. Bray, R. Reddy, J. Chen, S.L. Fisher, F.O. Ademuyiwa, L.J. Bierut.

306/9:15 Exploring choices among women undergoing panel-based genetic testing: A mixed-methods study. J. Shuldiner, G. Rodin, J. Knight, Y. Bombard, K. Metcalfe, J. Kotsopoulos, S. Ferguson, A. Tone, J. McCuaig, M. Bernardini.


Saturday, October 20

8:30 AM–9:30 AM

Concurrent Platform Session G

96. Leveraging the Cancer Genome Atlas

Room 6E, Upper Level, San Diego Convention Center

Moderators: Matthew Bainbridge, Rady Children's Hosp, San Diego
  Scott Newman, St Jude Children's Research Hosp, Memphis

 

307/8:30 Integrative epigenomics analyses identified a novel gene ELF1 associated with lung cancer. Y.X. Chen, Y.Y. Duan, H.M. Nui, Y. Rong, S. Yao, S.S. Dong, Y. Guo, T.L. Yang.

308/8:45 Germline genetic variants associated with immune response in colorectal cancer and their contribution to survival. J.R. Huyghe, T. Hamada, B. Banbury, T.A. Harrison, C.S. Grasso, K. Nosho, K. Inamura, M. Giannakis, R. Nishihara, L. Hsu, W. Sun, P.A. Newcomb, S. Ogino, A.T. Chan, U. Peters.

309/9:00 Germline variants associated with immune infiltration in solid tumors. S. Shahamatdar, M.X. He, E. Van Allen, S. Ramachandran.

310/9:15 Integrative genomic analyses to identify susceptibility genes for somatic mutations in human cancers. Z. Chen, J. Bao, W. Wen, J. Long, Q. Cai, X. Shu, W. Zheng, X. Guo.


Saturday, October 20

8:30 AM–9:30 AM

Concurrent Platform Session G

97. The Genetics and Genomics of Epilepsy

Room 6F, Upper Level, San Diego Convention Center

Moderators: Julie Korenberg, Univ Utah, Salt Lake City
  Ryan Collins, Harvard Med Sch, Cambridge

 

311/8:30 Pathogenic mutations in GABAergic transporters (GAT1, GAT3) and biosynthetic enzymes (GAD65, GAD67) cause a spectrum of genetic generalised epilepsy syndromes. S.K. Chung, K. Everett, E. Dudley, J.G. Mullins, I. Scheffer, S. Berkovic, M.I. Rees.

312/8:45 Evaluation of copy number burden in specific epilepsy types from a genome-wide study of 18,329 subjects. L.M. Niestroj, on behalf of the Epi25k Consortium.

313/9:00 De novo pathogenic variants in neuronal differentiation factor 2 (NEUROD2) cause a form of early infantile epileptic encephalopathy. A. Sega, E. Mis, K. Lindstrom, S. Andrews, W. Ji, M. Konstantino, M. Cho, J. Juusola, M. Khoka, S. Lakhani.

314/9:15 The genetic landscape of the developmental and epileptic encephalopathies. A.M. Muir, C.T. Myers, M.G. Mehaffey, K. Boysen, G. Hollingsworth, C. King, A. Schneider, A. Buttar, A. Chowdhary, A.B.I Rosen, M. Sud, N. Weed, J.X. Chong, M.J. Bamshad, D.A. Nickerson, UW Center for Mendelian Genomics, L.G. Sadleir, I.E. Scheffer, H.C. Mefford.


Saturday, October 20

9:45 AM–11:15 AM

Concurrent Platform Session H

98. Fine-mapping Using Statistical and Functional Tools

Ballroom 20A, Upper Level, San Diego Convention Center

Moderators: Jean Morrison, Univ Chicago
  Robert Maier, Massachusetts Gen Hosp, Boston

 

315/9:45 Large-scale trans-ethnic genome-wide association study reveals novel loci, causal molecular mechanisms and effector genes for kidney function. A.P. Morris, A. Akbarov, M. Tomaszewski, N. Franceschini, COGENT-Kidney Consortium.

316/10:00 High resolution fine mapping of 406 smoking/drinking loci via a novel method that synthesizes the analysis of exome-wide and genome-wide association statistics. Y. Jiang, the GWAS and Sequencing Consortium of Alcohol and Nicotine Use.

317/10:15 Fine-mapping of type 2 diabetes and glycemic traits with whole genome sequence data using 49,022 individuals from the NHBLI’s TOPMed WGS Program. A.K. Manning, D. Dicorpo, J. Wessel, TOPMed Diabetes Working Group.

318/10:30 Single-base resolution of autoimmune disease associations using molecular phenotypes. K. Kundu, S. Watt, A. Mann, K. De Lange, L. Vasquez, BLUEPRINT Consortium, L. Chen, J. Barrett, C. Anderson, N. Soranzo.

319/10:45 Fine-mapping causal regulatory variants using massively parallel reporter assays. N.S. Abell, M.K. DeGorter, M.J. Gloudemans, B. Balliu, K.S. Smith, S.B. Montgomery.

320/11:00 Inferring enhancer and noncoding RNA dysregulation underlying 2,419 UK Biobank phenotypes. A. Amlie-Wolf, L. Qu, E.E. Mlynarski, P.P. Kuksa, Y.Y. Leung, C.D. Brown, G.D. Schellenberg, L.S. Wang.


Saturday, October 20

9:45 AM–11:15 AM

Concurrent Platform Session H

99. Genetic and Epigenetic Effects on the Transcriptome

Ballroom 20BC, Upper Level, San Diego Convention Center

Moderators: Alexander Gusev, Dana Farber Cancer Inst, Harvard Sch Med, Cambridge
  Timothy Frayling, Univ Exeter, UK

 

321/9:45 The GTEx Consortium atlas of genetic regulatory effects across human tissues. T. Lappalainen, GTEx Consortium.

322/10:00 Leveraging gene expression to understand the consequences of polygenic risk scores for disease in healthy individuals. A. Claringbould, U. Võsa, H.-J. Westra, T. Esko, L. Franke, eQTLGen Consortium, BIOS Consortium.

323/10:15 The transethnic portability of predictive models for gene expression. K.L. Keys, A.C.Y. Mak, W. Eckalbar, M.J. White, C. Eng, D. Hu, S. Huntsman, J. Liberto, S. Oh, S. Salazar, J. Rodríguez-Santana, R. Hernandez, J. Ye, N. Zaitlen, E. Burchard, C.R. Gignoux.

324/10:30 Identifying novel epigenetic allele-specific expression effects in GTEx. S.N. Kravitz, W.C. Huang, E. Ferris, A.R. Quinlan, C. Gregg.

325/10:45 TIVAN: Tissue-specific cis-eQTL single nucleotide variant annotation and prediction. L. Chen, B. Yao, A. Mitra.

326/11:00 Predicting the impact of cis-regulatory variation on alternative polyadenylation. N. Bogard, J. Linder, A.B. Rosenberg, G. Seelig.


Saturday, October 20

9:45 AM–11:15 AM

Concurrent Platform Session H

100. Understanding the Brain with Computational Genomics

Ballroom 20D, Upper Level, San Diego Convention Center

Moderators: Yan Zhang, Ohio State Univ, Columbus
  Farhad Hormozdiari, Harvard Univ, Cambridge

 

This session is not eligible for continuing education credit.

 

327/9:45 Genetically regulated gene expression in brain and peripheral tissues types associated with PTSD. N.P. Daskalakis, M.S. Breen, S. van Rooij, J. Hartmann, K. Girdhar, CommonMind Consortium, PGC PTSD, T. Jovanovic, C. Nievergelt, H.K. Im, J.D. Buxbaum, P. Sklar, K.J. Ressler, E.A. Stahl, L.M. Huckins.

328/10:00 Dissecting the genetic, transcriptomic, and phenotypic complexity of PTSD across 9400 individuals and 30 million phenotypic observations. Y. Li, V. Michopoulos, A. Lori, A. Lott, B. Bradley, T. Jovanovic, K. Ressler, M. Kellis, N. Daskalakis.

329/10:15 Comprehensive functional genomic resource and integrative model for the adult brain. D. Wang, S. Liu, J. Warrell, H. Won, X. Shi, F. Navarro, D. Clarke, M. Gu, P. Emani, M. Xu, Y. Yang, J. Park, S. Rhie, K. Manakongtreecheep, H. Zhou, A. Nathan, J. Zhang, M. Peters, E. Mattei, D. Fitzgerald, T. Brunetti, J. Moore, N. Sestan, A. Jaffe, K. White, Z. Weng, D. Geschwind, J. Knowles, M. Gerstein, PsychENCODE Consortium.

330/10:30 Single-cell transcriptomic catalog of mouse cortical development. J.M. Simon, L. Loo, L. Xing, E.S. McCoy, J.K. Niehaus, J. Guo, E.S. Anton, M.J. Zylka.

331/10:45 Machine learning of ultra-deep whole-genome sequencing of human brain reveals somatic retrotransposition in both neurons and glia. X. Zhu, B. Zhou, R. Pattni, K. Gleeson, C. Tan, S. Steven, A. Fiston-Lavier, J. Lennington, L. Tomasini, T. Bae, L. Faching, MP. Snyder, D. Petrov, A. Abyzov, FM. Vaccarino, BA. Barres, OH. Vogel, C. Tamminga, DF. Levinson, AE. Urban.

332/11:00 Using sequence graphs to fully characterize the variability of pathogenic repeat loci. E. Dolzhenko, F. Schlesinger, V. Deshpande, J.J.F.A. van Vugt, G. Narzisi, S. Chen, C. Reeves, L. Winterkorn, N.S. Wexler, J.H. Veldink, R.J. Taft, D.R. Bentley, M.A. Eberle, The US-Venezuela Collaborative Research Group.


Saturday, October 20

9:45 AM–11:15 AM

Concurrent Platform Session H

101. Novel Approaches for Conducting Genome-wide Association Studies

Room 6A, Upper Level, San Diego Convention Center

Moderators: Ece Uzun, Brown Univ Alpert Med Sch, Providence
  Ryan Minster, Univ Pittsburgh

 

333/9:45 Genome-wide analyses identify CTNNA2 and SULT2A1 as candidate genes for cleft palate only in the African population. A. Butali, P.A. Mossey, W.L. Adeyemo, M.A. Eshete, L.J.J. Gowans, M.L. Marazita, J.C. Murray, A.A. Adeyemo.

334/10:00 Quantifying genetic risk of prosthetic joint infection through biobank data and electronic health records. D.J. McGuire, D. Liu.

335/10:15 Optimization of high diversity imputation in cohort of more than 400,000 US veterans in the VA’s Million Veteran Program (MVP). Y. Shi, S. Ji, S. Gallagher, B. Gorman, J. Prescott, J. Huang, C. Pan, T. Assimes, S. Muralidhar, C. O’Donnell, E. Hauser, H. Zhao, P. Tsao, S. Pyarajan.

336/10:30 Expanding the scope of the GWAS catalog to improve drug target identification and prioritisation. A. Buniello, O. Vrousgou, E. Mountjoy, J. Hayhurst, L. Harris, C. Malangone, J. MacArthur, T. Burdett, M. Ghoussaini, J. Barrett, I. Durham, H. Parkinson, F. Cunningham.

337/10:45 Joint analysis of phenotypes enables pathway detection. H. Julienne, V. Laville, C. Lasry, A. Ziyatdinov, P. Kraft, P. Lechat, H. Ménager, B. J. Vilhjálmsson, V. Guillemot, H. Aschard.

338/11:00 A systematic classification of heritable risk factors influencing common diseases. A. Cortes, C. Dendrou, L. Fugger, G. McVean.


Saturday, October 20

9:45 AM–11:15 AM

Concurrent Platform Session H

102. Increasing Functional Resolution Through Single Cell Analysis

Room 6B, Upper Level, San Diego Convention Center

Moderators: Nick Banovich, Translational Genomics Res Inst, Phoenix
  Mingyao Li, Univ Pennsylvania, Philadelphia

 

339/9:45 Measuring gene expression inequality in single cells using adjusted Gini index. X. Zheng, C. Green, A. Shami, Q. Ma, S. Hammoud, J. Li.

340/10:00 Decomposing cell identity for transfer learning across omics, tissues, and species. G.L. Stein-O'Brien, B.S. Clark, T. Sherman, S. Blackshaw, E.J. Fertig, L.A. Goff.

341/10:15 Detecting differential splicing events from single-cell RNA sequencing data with or without unique molecular identifiers. Y. Hu, N.R. Zhang, M. Li.

342/10:30 Identification of meiotic recombination events through gamete genome reconstruction by linked-read sequencing technology. Z. Chong, P. Xu.

343/10:45 Determining KIR repertoires using single cell transcriptomics. A. Goncalves, R. Vento-Tormo, M. Efremova, S.A. Teichmann.

344/11:00 Single-cell co-expression network demonstrated superior biological signal in tissue-specific network analyses. T. Li, A. Kim, A. Battle, L. Kasper.


Saturday, October 20

9:45 AM–11:15 AM

Concurrent Platform Session H

103. Evaluating the Yield of Genetic Testing in Diverse Settings

Room 6C, Upper Level, San Diego Convention Center

Moderators: Jane Juusola, GeneDx, Gaithersburg
  Ross Rowsey, Mayo Clinic, Rochester

 

345/9:45 Systematic evaluation of yields from whole-genome sequencing of 8,954 individuals compared to conventional technologies for prenatal and pediatric diagnostics. H. Brand, C. Lowther, B.B. Currall, J.L. Giordano, V. Aggarwal, H.Z. Whang, X. Zhao, D. Lucente, L. Margolin, J-Y. An, D.M. Werling, S. Dong, S.J. Sanders, B. Devlin, K. Gilmore, B. Powell, A. Brandt, A.H. O'Donnell-Luria, N.J. Lennon, D.B. Goldstein, H.L. Rehm, D. MacArthur, N.L. Vora, B. Levy, R. Wapner, M.E. Talkowski.

346/10:00 Low-pass whole-genome sequencing: A study of 1,090 recurrent miscarriage couples. Z. Dong, J. Yan, F. Xu, J. Yuan, H. Wang, T.Y. Leung, S.W. Cheung, C.C. Morton, H. Jiang, Z.J. Chen, K.W. Choy.

347/10:15 Whole exome sequencing as a tool for the diagnosis of inborn errors of metabolism in cohort of 550 patients with ID and developmental defect. J. Delanne, N. Houcinat, S. Moutton, A.L. Bruel, S. Nambot, P. Callier, A. Sorlin, P. Callier, N. Jean-Marçais, A.L. Mosca-Boidron, F. Tran Mau-Them, D. Lehalle, S. El Chehadeh, C. Francannet, M. Lebrun, L. Lambert, M.L. Jacquemont, M. Gérard-Blanluet, J.L. Alessandri, M. Willems, F. Feillet, T. O'Grady, Y. Duffourd, C. Philippe, L. Faivre, C. Thauvin-Robinet.

348/10:30 Frequency and features of incidental findings across 12,702 eMERGE network participants. A.S. Gordon, H. Zouk, E. Venner, M.S. Leduc, L. Witkowski, C.M. Eng, B.H. Funke, L.M. Amendola, D.S. Carrell, R.L. Chisholm, W.K. Chung, R.C. Green, H. Hakonarson, I.J. Kullo, E.B. Larson, K.A. Leppig, D.M. Muzny, N.J. Lennon, C.A. Prows, L.J. Rasmussen-Torvik, M.E. Smith, I.B. Stanaway, S.L. Van Driest, K. Walker, G.L. Wiesner, M.S. Williams, D.R. Crosslin, R.A. Gibbs, H.L. Rehm, G.P. Jarvik, The Electronic Medical Records and Genomics (eMERGE) Network.

349/10:45 Microbial detection in rapid whole genome sequencing in an acute care setting. M.N. Bainbridge, E. Sanford, L. Farnaes, M. Wright, D. Dimmock, S. Kingsmore.

350/11:00 Genetic testing for healthy individuals: A medically actionable panel finds a high positive rate for hereditary disease. E. Haverfield, E.D. Esplin, S. Aguilar, K.E. Ormond, A. Hanson-Kahn, S. Macklin, C. Sak, S. Bleyl, P. Atwal, C. Fine, P.J. Hulick, O.K. Gordon, J. Gu, L. Velsher, M. Duquette, R.L. Nussbaum, S. Aradhya.


Saturday, October 20

9:45 AM–11:15 AM

Concurrent Platform Session H

104. Discoveries in Syndromic and Non-syndromic Congenital Heart Disease

Room 6D, Upper Level, San Diego Convention Center

Moderators: Francois Bernier, Alberta Children's Hosp Res Inst, Univ Calgary, Canada
  Taila Hartley, Children's Hosp Eastern Ontario Res Inst, Ottawa, Canada

 

351/9:45 A deep learning framework identifies a role for noncoding de novo variants in congenital heart disease. F. Richter, K.M. Chen, J. Zhou, S. Morton, A. Kitaygorodsky, H. Qi, N. Patel, K.B. Manheimer, E.E. Schadt, J.W. Newburger, E. Goldmuntz, M. Brueckner, G.A. Porter, R.W. Kim, D. Srivastava, D. Bernstein, M. Tristani-Firouzi, J. Yost, M. Yandell, Y. Shen, W.K. Chung, J.G. Seidman, C.E. Seidman, O.G. Troyanskaya, B.D. Gelb.

352/10:00 Biallelic truncating mutations in TMEM94 are associated with neurodevelopmental delay, congenital heart defects and distinct facial dysmorphism. J. Stephen, S. Maddirevula, S. Nampoothiri, M. Herzog, J.D. Burke, A. Shukla, K. Steindl, A. Eskin, S.J. Patil, P. Joset, H. Lee, L.J. Garrett, T. Yokoyama, N. Balanda, A. Elkahloun, A. Zheng, K.M. Girisha, C. Rivas, G. Ramantani, S.M. Wakil, L. Mahmoud, A.B. Kulkarni, T. Ben-Omran, D. Colak, H.D. Morris, A. Rauch, F.S. Alkuraya, J.A. Martinez-Agosto, W. Gahl, M.C.V. Malicdan, Undiagnosed Diseases Network members.

353/10:15 Variants in MAP4K4 cause a novel and potentially treatable form of neurologic dysfunction with cardiac anomalies. E.J. Bhoj, D. Li, M.H. Harr, R. Smith, S. Ellingwood, M. Cho, J. Keller-Ramey, R. Person, A. Sidhu, S. Saliganan, S.L. Cassisi, D.K. Grange, X. Hu, Y. Shen, M. Maimaiti, Y. Luo, H.H. Hakonarson.

354/10:30 De novo variants in congenital diaphragmatic hernia identify MYRF as a new syndrome and reveal genetic overlaps with other developmental disorders. X. Zhou, H. Qi, L. Yu, J. Wynn, H. Zhao, Y. Guo, N. Zhu, A. Kitaygorodsky, R. Hernan, G. Aspelund, V. Duron, F.Y. Lim, T. Crombleholme, R. Cusick, K. Azarow, M.E. Danko, D. Chung, B.W. Warner, G.B. Mychaliska, D. Potoka, A.J. Wagner, M. ElFiky, J.M. Wilson, D. Nickerson, M. Bamshad, F.A. High, M. Longoni, P.K. Donahoe, W.K. Chung, Y. Shen.

355/10:45 Hypomorphic mutations in the deubiquitilation enzyme OTUD5 lead to multiple congenital defects. D.B. Beck, H. Oda, A. Asmar, N. Sampaio Moura, E. Macnamara, P. D'Souza, J. Bodurtha, M. Walkiewicz, R. Wang, C.J. Tifft, I. Aksentijevich, D. Kastner.

356/11:00 Heterozygous missense mutations in CDK8, a regulator of the Mediator complex, cause a syndromic developmental disorder. E. Calpena, S.M.A. Swagemakers, J.A.C. Goos, T. Kaserer, O. Popoola, M.J. Ortiz Ruiz, T. Barbaro Dieber, L. Bownass, E. Brilstra, E. Brimble, N. Foulds, T.A. Grebe, A.V.E. Harder, M.M. Lees, K. McWalter, R.A. Newbury-Ecob, K.R. Ong, D. Osio, F.J. Reynoso Santos, M.R.Z. Ruzhnikov, E. Torti, E. van Binsbergen, M.F. van Dooren, D.D.D. Study, P.J. van der Spek, J. Blagg, S.R.F. Twigg, I.M.J. Mathijssen, P. Clarke, A.O.M. Wilkie.


Saturday, October 20

9:45 AM–11:15 AM

Concurrent Platform Session H

105. Human Reproduction and Fertility

Room 6E, Upper Level, San Diego Convention Center

Moderators: Jessica Schuster, Women & Infants Hosp, Providence
  Alexander Yatsenko, Univ Pittsburgh

 

357/9:45 Uncovering novel cytogenetic and molecular etiologies for male infertility. S.L.P. Schilit, S. Menon, T. Kammin, E. Wilch, C. Redin, S. Jiang, A.J. MacQueen, J.F. Gusella, M.E. Talkowski, C.C. Morton.

358/10:00 Ectopically expressed CGG repeats lead to ovarian dysfunction in a mouse model of the FMR1 premutation. K.E. Shelly, N.R. Candelaria, D.L. Nelson.

359/10:15 Largest genome-wide association meta-analysis of endometriosis and its subphenotypes including 21K cases and 482K controls reveals 21 loci for the condition and genetically based comorbidity with various pain conditions. N. Rahmioglu, S. Mortlock, K. Banasik, R. Mägi, L. Stefansdottir, C. Turman, A. Giri, O. Uimari, Y. Sapkota, S. Macgregor, B. Marciniak, S.K. Low, D. Strapagiel, A. Campbell, C. Hayward, R. Danning, T. D’hooghe, D. Nyholt, P. Rogers, C. Becker, D. Chasman, P. Kraft, D. Whiteman, D.V. Edwards, V. Steinthorsdottir, M. Nyegaard, G. Montgomery, S. Missmer, A.P. Morris, K.T. Zondervan, The International Endometriosis Genomics Consortium (IEGC).

360/10:30 Endometriosis genome-wide association study in >288,000 women of European ancestry. G. Galarneau, P. Fontanillas, T. Hu-Seliger, C. Clementi, U. Schick, D. Colaci, D.E. Parfitt, J.Y. Tung, P. Yurttas Beim, the 23andMe Research Team, the Celmatix Research Team.

361/10:45 Genome-wide association analysis identifies 27 novel loci associated with uterine leiomyomas revealing common genetic origins with endometriosis. N. Mäkinen, C.S. Gallagher, H.R. Harris, O. Uimari, K.L. Terry, D.I. Chasman, S. Missmer, K.T. Zondervan, C.C. Morton, the 23andMe Research team, the FibroGENE consortium.

362/11:00 Exome sequencing of a Mayer-Rokitansky-Kuster-Hauser cohort reveals novel candidate genes and significant mutational burden. A. Jolly, Z. Coban Akdemir, S. N. Jhangiani, D. M. Muzny, A. Koch, J. E. Dietrich, I. B. Van den Veyver, S. Brucker, R. A. Gibbs, J. R. Lupski, J. E. Posey.


Saturday, October 20

9:45 AM–11:15 AM

Concurrent Platform Session H

106. Genetics of Growth and Lifespan

Room 6F, Upper Level, San Diego Convention Center

Moderators: Hailiang Huang, Stanley Ctr Psychiatric Res, Boston
  Anne O'Donnell-Luria, Broad Inst, Cambridge

 

This session is not eligible for continuing education credit.

 

363/9:45 Genetic study of longitudinal pubertal height growth describes links with adult health. D. Cousminer, Early Growth Genetics (EGG) Consortium.

364/10:00 Identifying novel longevity-associated variants from >90,000 whole-exome sequences of the DiscovEHR cohort. P. Sin-Chan, A.H. Li, C. Gao, C. O'Dushlaine, J.G. Reid, J.D. Overton, D.H. Ledbetter, D.J. Carey, A. Baras, A.N. Economides, A.R. Shuldiner.

365/10:15 Large-scale genome-wide discovery and phenome-wide association analyses of genetic differences in leukocyte telomere length. C. Li, L.A. Lotta, T. Loe, V. Codd, J. Tao, R.A. Scott, I.D. Stewart, N.D. Kerrison, F.R. Day, J. Luan, J.H. Zhao, C.P. Nelson, K. Ong, G. Matullo, J. Danesh, A. Butterworth, N. Samani, E.L. Denchi, N.J. Wareham, C. Langenberg, ENGAGE Consortium Telomere Group, EPIC-CVD Consortium, EPIC-InterAct Consortium.

366/10:30 Genomic underpinnings of lifespan allow prediction and reveal basis in modern risks. P.R.H.J. Timmers, N. Mounier, K. Läll, K. Fischer, Z. Ning, X. Feng, A. Bretherick, D.W. Clark, X. Shen, T. Esko, Z. Kutalik, J.F. Wilson, P.K. Joshi.

367/10:45 Mitochondrial variants influence human complex diseases and molecular endophenotypes. E. Yonova-Doing, C. Calabrese, N. Cai, I.D. Stewart, W. Wei, S. Karthikeyan, W.J. Astle, B. Prins, J. Peters, T. Jiang, P. Surendran, O. Stegle, T. Bolton, C. Langenberg, A. Wood, A.S. Butterworth, J. Danesh, N. Soranzo, P.F. Chinnery, J.M.M. Howson.

368/11:00 Mitochondrial DNA heteroplasmy is associated with overall mortality. R.J. Longchamps, Y.S. Hong, C.E. Newcomb, J.A. Sumpter, M.L. Grove, J.D. Walston, B.G. Windham, J. Coresh, E. Boerwinkle, E. Guallar, D.E. Arking.


Saturday, October 20

11:30 AM–11:40 AM

107. Announcement of the Winners of the Charles J. Epstein Trainee Awards for Excellence in Human Genetics Research

Hall C, Ground Level, San Diego Convention Center

ASHG provides merit-based research awards for trainees (predoctoral and postdoctoral, including genetic counseling trainees) on the basis of submitted, competitive abstracts and on-site presentations at the 2018 Annual Meeting. This year’s 6 winners will be announced.

 


Saturday, October 20

11:40 AM–1:00 PM

108. Featured Plenary Abstract Session III

Hall C, Ground Level, San Diego Convention Center

Moderators: Andrew T. DeWan, ASHG 2018 Program Committee
  Erica E. Davis, ASHG 2018 Program Committee

 

Featured Plenary Abstract Sessions include a diverse set of presentations selected from the top-rated abstracts across all topics.

 

369/11:40 Directly measuring the dynamics of the human mutation rate by sequencing large, multi-generational pedigrees. T. Sasani, B. Pedersen, A. Quinlan, M. Leppert, L. Baird, L. Jorde.

370/12:00 Genome-scale capture C promoter interaction analysis implicates novel effector genes at GWAS loci for bone mineral density. A. Chesi, Y. Wagley, M.E. Johnson, M. Manduchi, C. Su, S. Lu, M.E. Leonard, K.M. Hodge, J.A. Pippin, K.D. Hankenson, A.D. Wells, S.F.A. Grant.

371/12:20 Comprehensive analysis of alternative splicing across tumors from 8,705 patients. K. Lehmann, A. Kahles, N. Toussaint, M. Hüser, S. Stark, T. Sachsenberg, O. Stegle, O. Kohlbacher, C. Sander, G. Rätsch, The Cancer Genome Atlas Research Network.

372/12:40 Uganda genomes resource enables inferences into population history and genomic discovery in Africa. D. Gurdasani, T. Carstensen, S. Fatumo, G. Chen, CS. Franklin, J. Prado-Martinez, H. Bouman, Uganda Genomes Resource Investigators.