All Numbered Sessions Listing

Tuesday, October 15

1:00 PM–3:00 PM

Concurrent Invited Session I: Non-CME

1. ASHG/ESHG Building Bridges: Potential Policy Implications of Genetic Research into Educational Attainment

Grand Ballroom A, Level 3, Convention Center

Moderators: Kiran Musunuru, ASHG
  Joris Veltman, ESHG

 

Recent genome-wide association studies (Lee et al., Nature Genetics, 2018) have shown that polygenic scores composed of common variants can explain ~13% of the variance in educational attainment, and this number is set to increase as studies grow. While there has been considerable discussion in policy circles and the media about the ethics of gene editing, the implications of genetic prediction for behavioral and cognitive traits have received less attention. There is an urgent need to consider whether and how the findings from these studies should be applied in public policy. For example, should polygenic scores for educational attainment be used as a component of school admissions processes, or to identify children likely to need particular educational help? What threshold of precision would be necessary for useful deployment? Should we allow antenatal embryo selection based on these scores in IVF clinics? Should insurers be allowed to use polygenic scores in determining policy pricing? What are the potential unintended consequences of such policies, and what does the public think about them? How does knowledge about the heritability of educational attainment affect political notions of equality? How can we stop this debate being hijacked by extremist groups? In this session, genetics and policy experts will present the latest research on these topics and hold a panel discussion.

ESHG logo
ASHG logo

 

1:00 PM   Introduction. A.I. Young. Univ Oxford, UK.

1:10 PM   Polygenic prediction of education: U.S. attitudes regarding when and how it should be deployed. D. Conley. Princeton Univ.

1:20 PM   Genetics of education and egalitarian policy goals. K.P. Harden. Univ Texas Austin.

1:30 PM   Educational reform, ability, and labor market screening. A. Okbay. Vrije Univ Amsterdam, Netherlands.

1:40 PM   Lost in translation: Bias and methodological challenges in policy applications of polygenic educational scores. M. Mills. Univ Oxford, UK.

1:50 PM   Panel discussion.


Tuesday, October 15

1:00 PM–3:00 PM

Concurrent Invited Session I: Non-CME

2. Deep Learning for Interpretation of Human Genetic Variation

Grand Ballroom B, Level 3, Convention Center

Moderators: Anshul Kundaje, Stanford Univ
  Alexis Battle, Johns Hopkins Univ, Baltimore

 

A major barrier to the adoption of sequencing in clinical practice is the challenge of interpreting the consequences of genetic variants. Recent advances in deep learning in genomics have led to new classes of models for predicting the molecular and clinical effects of both noncoding and protein-altering variation, which have the potential to complement traditional statistical and bioinformatics methods. This session will showcase the potential for deep neural networks to interpret functional genetic variation and provide new biological insights by learning to extract relevant features directly from sequence. We will also highlight the challenges for this rapidly growing field, particularly around interpretation of models, and the vast quantities of relevant datasets required for successful training of deep neural networks.

 

1:00 PM   Decoding the role of regulatory variation in human disease with deep learning methods. O. Troyanskaya. Princeton Univ.

1:20 PM   Unsupervised deep learning for interpretation of human genetic variation. D. Marks. Harvard Med Sch, Boston.

1:40 PM   Learning the splicing code from primary sequence with deep learning. K. Farh. Illumina Inc, Foster City.

2:00 PM   Sequential regulatory activity prediction across chromosomes enables effective disease association analyses. D. Kelley. Calico Inc, South San Francisco.

2:20 PM   Panel discussion.


Tuesday, October 15

1:00 PM–3:00 PM

Concurrent Invited Session I: Non-CME

3. Genetics on Target: The Role of Genetic Evidence in Drug Discovery and Development, from Vision to Reality

Grand Ballroom C, Level 3, Convention Center

Moderator: Robert A. Scott, Glaxo Smith Kline, Stevenage, UK

 

The considerable efforts in the human genetics community to identify genomic regions associated with susceptibility to disease has, in large part, been motivated by the potential to identify putative therapeutic targets. However, it remains unclear whether the vast number of associations being identified will translate to a wealth of therapeutic targets. Our panel of speakers have extensive experience in both academia and industry that allows them to reflect on the utility of genetics in drug discovery and development. The session includes six short talks from leading members of the industry and academic communities, followed by a panel discussion. Across the talks, we aim to cover six key themes that complement the overarching aim to provide the community with more insight into what it takes to practically use genetics to guide drug development from target discovery to late-stage validation. These themes are: (1) defining the case for genetics-based drug development; (2) describing how large-scale biobanks can help realise the vision; (3) discussing whether we could extend the idea too far and go wrong by an undue focus on genetics; (4) outlining what is needed to motivate a drug discovery program after finding an association; (5) detailing an ongoing example of a genetically-validated target program from identification to validation; and (6) realizing the vision for genetics-based drug development - what will it really take and how do we get there? We will dedicate the second hour to a panel discussion where the audience and panel will have the chance to respond to each theme and ask questions.

 

1:00 PM   The case for routine integration of genetic evidence into drug development. R. Plenge. Celgene, Cambridge.

1:15 PM   The role for large-scale population studies in enabling genetically-driven drug development. J.P. Casas. VA Healthcare Boston.

1:30 PM   A good idea gone too far? The appropriate role for genetic evidence in drug discovery. M. Nelson. GSK, Collegeville.

1:45 PM   So, we've found a genetic association: What next? S. John. Biogen, Cambridge.

2:00 PM   Developing a genetically-validated target, through target identification, validation to clinical trial design. J. Hutz. Eisai AiM Inst, Andover.

2:15 PM   Realizing the vision of genetically-driven drug development: What will it take and how do we get there? D. Altshuler. Vertex Pharmaceuticals, Boston.

2:30 PM   Panel discussion.


Tuesday, October 15

3:30 PM–4:00 PM

4. ASHG Welcome and Presidential Address: An Unexceptional President

Hall B, Level 1, Convention Center

The Presidential Address will tie together the thesis of the Presidential Symposium on genetic exceptionalism with the exciting changes that are now underway with the Strategic Plan and the evolution of the governance and transparency of the Society. This address is coupled to the symposium because of my very deliberate and wide-ranging efforts to maximize the input from, engagement with, and benefits, to the members of ASHG. The governance of our Society must be centered on you, the members, not any one person as a leader. An unexceptional President effects the priorities and the needs of the members into a forward-looking vision that enables the best human genetics and genomics research.

2019 President

Leslie G. Biesecker, M.D.
Leslie G. Biesecker, MD

 


Tuesday, October 15

4:00 PM–4:05 PM

5. C.W. Cotterman Awards Presentation

Hall B, Level 1, Convention Center

Presented by Bruce Korf, MD, PhD, Editor-in-Chief. 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.

 


Tuesday, October 15

4:05 PM–4:20 PM

6. ASHG Early Career Award Presentation and Lecture: Using Gene Expression to Interpret Common and Rare Genetic Diseases

Hall B, Level 1, Convention Center

Introduction: Carlos Bustamante, PhD, Stanford University

Stephen Montgomery, PhD, has worked on gene regulation and expression and its intersection with human genetics. He gained tenure in 2018 from Stanford, after joining faculty as an assistant professor in 2011. His lab has collaborated with many teams and consortia to advance the use of functional genomics to interpret the mechanisms of genetic disease.

Recipient

Stephen Montgomery, PhD
Stephen Montgomery, PhD, Stanford University School of Medicine

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

 


Tuesday, October 15

4:20 PM–4:50 PM

7. ASHG William Allan Award Presentation and Lecture: Know Thy Genome

Hall B, Level 1, Convention Center

Introduction: Haig H. Kazazian, MD, Johns Hopkins University

Stylianos Antonarakis, MD, DSc, is a medical, molecular, and human geneticist, and a physician-scientist whose life’s work revolves around understanding the human genome and the relation of its variation with Mendelian and polygenic disorders. Dr. Antonarakis’ contributions to the field focus on the genetic basis of Mendelian and complex genetic disease, chromosome 21 biology and Down syndrome, and the genetic factors underlying variation in gene expression and regulation.

Recipient

Stylianos Antonarakis, MD, DSc
Stylianos Antonarakis, MD, DSc, University of Geneva

The William Allan Award recognizes substantial and far-reaching scientific contributions to human genetics, and 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.

 


Tuesday, October 15

4:50 PM–6:00 PM

8. Featured Plenary Abstract Session I

Hall B, Level 1, Convention Center

Moderators: Kiran Musunuru, ASHG 2019 Program Chair
  Teri A. Manolio, ASHG 2019 Program Committee

 

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

 

1/4:50 High-depth genome sequencing in diverse African populations reveals the impact of ancestral migration, cultural demography, and infectious disease on the human genome. N.A. Hanchard, A. Choudhury, S. Aron, L. Botigue, D. Sengupta, G. Botha, T. Bensellak, G. Wells, J. Kumuthini, D. Shriner, Y. Jaufeerally Fakim, A. Wahed Ghoorah, E. Dareng, T. Odia, D. Falola, E. Adebiyi, S. Hazelhurst, G. Mazandu, O.A. Nyangiri, M. Mbiyavanga, S. Kassim, N. Mulder, S.N. Adebamowo, E.R. Chimusa, C. Rotimi, M. Ramsay, A. Adeyomo, Z. Lombard, as members of the H3Africa Consortium.

2/5:10 Pathogenic, loss-of-function mutations in MRAP2 cause metabolic syndrome. A. Bonnefond, M. Baron, J. Maillet, M. Huyvaert, R. Boutry, G. Charpentier, M. Tauber, R. Roussel, B. Balkau, M. Marre, M. Canouil, P. Froguel.

3/5:30 Exome sequencing of 25,000 schizophrenia cases and 100,000 controls implicates 10 risk genes, and provides insight into shared and distinct genetic risk and biology with other neurodevelopmental disorders. T. Singh, B.M. Neale, M.J. Daly, on behalf of the SCHEMA consortium.


Wednesday, October 16

9:00 AM–10:00 AM

Concurrent Platform Session A

9. Genetics of Addiction and Behavior

Hall B, Level 1, Convention Center

Moderators: Jeremiah Scharf, Massachusetts Gen Hospital, Boston
  Sarah Medland, QIMR Berghofer, Brisbane, Australia

 

4/9:00 Genome-wide meta-analysis of alcohol use disorder and problematic drinking identifies over 30 risk variants. H. Zhou, S. Sanchez-Roige, T.K. Clarke, J.M. Sealock, R. Polimanti, R.L. Kember, R.V. Smith, A.C. Justice, L.K. Davis, A.A. Palmer, H.R. Kranzler, J. Gelernter, on behalf of the VA Million Veteran Program.

5/9:15 Trans-ancestry GWAS meta-analysis of tobacco and alcohol use. M. Liu, Trans-Omics for Precision Medicine; GWAS & Sequencing Consortium of Alcohol and Nicotine use.

6/9:30 The functional landscape and essential genes discovery in genetic etiology of tobacco use. F. Chen, Y. Jiang, D.J. Liu.

7/9:45 Obesity-associated variants in the FTO locus: Dissecting the complex landscape of GWAS. D. Sobreira, I. Aneas, A. Joslin, M. Nobrega.


Wednesday, October 16

9:00 AM–10:00 AM

Concurrent Platform Session A

10. Novel Discoveries in Large-Scale Genome-Wide Association Studies

Grand Ballroom A, Level 3, Convention Center

Moderators: Han Chen, Univ Texas Hlth Sci Cent Houston
  Jean Morrison, Univ Chicago

 

8/9:00 Genome-wide association study on vitamin D levels in 482,619 Europeans reveals 47 novel vitamin D-related loci. D. Manousaki, R. Mitchel, T. Dudding, S. Haworth, V. Forgetta, N.J. Timpson, J.B. Richards.

9/9:15 A large cross-ancestry meta-analysis of genome-wide association studies identifies novel risk loci for primary open-angle glaucoma, and shows a genetic link to Alzheimer’s disease. P. Gharahkhani, E. Jorgenson, P. Hysi, A. Khawaja, S.A. Pendergrass, X. Han, A. Hewitt, R. Igo, H. Choquet, N. Josyula, D. Mackey, C.P. Pang, F. Pasutto, P. Mitchell, P. Bonnemaijer, A. Lotery, N. Pfeiffer, A. Palotie, C. van Duijn, J. Haines, C. Hammond, M. Hauser, L. Pasquale, C.C.W. Klaver, M. Kubo, T. Aung, J.E. Craig, S. MacGregor, J. Wiggs, International Glaucoma Genetics Consortium, NEIGHBORHOOD consortium, ANZRAG study, FinnGen study.

10/9:30 Near-optimal trans-ethnic association and fine mapping of smoking associated genes integrating GWAS and TOPMed sequence data of 1.3 million individuals. Y. Jiang, TOPMed smoking working group and GSCAN consortium.

11/9:45 Genetics of 38 blood and urine biomarkers in the UK Biobank. N. Sinnott-Armstrong, Y. Tanigawa, S. Naqvi, N.J. Mars, D. Amar, H.M. Ollila, M. Aguirre, G.R. Venkataraman, M. Wainberg, J.P. Pirruccello, J. Qian, A. Shcherbina, F. Rodriguez, T.L. Assimes, V. Agarwala, R. Tibshirani, T. Hastie, S. Ripatti, M.J. Daly, J.K. Pritchard, M.A. Rivas, FinnGen.


Wednesday, October 16

9:00 AM–10:00 AM

Concurrent Platform Session A

11. Better Genome References and Representations

Grand Ballroom B, Level 3, Convention Center

Moderators: Gill Bejerano, Stanford Univ
  Alexis Norris, USFDA, Glen Rock

 

12/9:00 Advancements in the human genome reference assembly (GRCh38). T. Rezaie, K. Howe, T. Graves-Lindsay, P. Flicek, V.A. Schneider, the Genome Reference Consortium.

13/9:15 Constructing a reference genome that captures global genetic diversity for improved interpretation of whole genome sequencing data. K.H.Y. Wong, W. Ma, N. Wei, E.C. Yeh, W.J. Lin, E.H.F. Wang, J.P. Su, F.J. Hsieh, Y. Mostovoy, M. Levy-Sakin, S. Chow, E. Young, C. Chu, A. Poon, M. Xiao, P.Y. Kwok.

14/9:30 Development of sequence variation graphs and graph-based software for genomics studies. S. Tetikol, V. Semenyuk, A. Dolgoborodov, A. Jain, J. Browning, I. Johnson, D. Turgut, O. Kalay, D. Kabakci, Graph Development Team.

15/9:45 Candidate variant discovery using graph genomes: Leveraging familial genetic structures to improve detection of causal variation to rare diseases. C. Markello, J. Eizenga, A. Novak, E. Garrison, G. Hickey, J. Siren, X. Chang, J. Sibbesen, J. Monlong, R. Rounthwaite, B. Pusey, T. Markello, C. Lau, D. Adams, W. Gahl, B. Paten.


Wednesday, October 16

9:00 AM–10:00 AM

Concurrent Platform Session A

12. Large-scale Proteome and Metabolome Studies

Grand Ballroom C, Level 3, Convention Center

Moderators: Guillaume Pare, McMaster Univ, Hamilton, Canada
  Julia El-Sayed Moustafa, King's Col London, UK

 

16/9:00 Genetic control of the human brain proteome. C. Robins, W. Fan, D. Duong, J. Meigs, E. Gerasimov, D. Cutler, E. Dammer, P. De Jager, D. Bennett, J. Lah, A. Levey, N. Seyfried, A. Wingo, T. Wingo.

17/9:15 Genomic architecture of 184 plasma proteins in 20,000 individuals: The SCALLOP Consortium. J. Wilson, E. Macdonald-Dunlop, P.K. Joshi, J.E. Peters, L. Folkersen, I. Ingelsson, K. Michaelsson, S. Gustafsson, S. Enroth, A. Johansson, G. Smith, D. Zhernakova, A. Siegbahn, A. Kalnapenkis, N. Eriksson, J. Fu, L. Franke, C. Hayward, L. Wallentin, T. Esko, E. Zeggini, C. Teunissen, O. Hansson, P. Eriksson, U. Gyllensten, A.S. Butterworth, A. Mälarstig, on behalf of the SCALLOP Consortium.

18/9:30 A genome-wide association study reveals 51 novel loci of human metabolome in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). E.V. Feofanova, H. Chen, Q. Qi, R.C. Kaplan, M.L. Grove, K.E. North, Y. Dai, P. Jia, C.C. Laurie, M. Daviglus, J. Cai, E. Boerwinkle, B. Yu.

19/9:45 Quantitative proteomics as a complementary diagnostic tool for Mendelian disorders. R. Kopajtich, C. Ludwig, C. Mertes, C. Meng, V.A. Yépez, L.S. Kremer, M. Gusic, A. Nadel, D. Smirnov, J. Behr, K. Murayama, T.M. Strom, B. Küster, J.A. Mayr, D. Rokicki, S. Wortmann, J. Gagneur, H. Prokisch.


Wednesday, October 16

9:00 AM–10:00 AM

Concurrent Platform Session A

13. Research Participants' Experiences and Preferences

Room 310A, Level 3, Convention Center

Moderators: John Carey, Univ Utah, Salt Lake City
  Kristen M. Wigby, Rady Children's Inst Gen Med, San Diego

 

20/9:00 Patient and public preferences on being recontacted with updated genomics results: A mixed methods study. Y. Bombard, A. Sebastian, C. Mighton, M. Clausen, S. Muir, S. Shickh, N. Baxter, A. Scheer, T.H. Kim, D. Regier, E. Glogowski, K. Schrader, R.H. Kim, J. Lerner-Ellis, A. Bayoumi.

21/9:15 Participant perceptions on return of secondary findings in a clinical research setting: Low decisional conflict and potential need for targeted education and counseling. M. Similuk, J. Yan, L. Jamal, M. Walkiewicz, M. Lenardo, H. Su.

22/9:30 Variation in intention to participate in genetic research among Hispanic/Latinx populations by Latin America birth-residency concurrence: A global study. J.G. Perez-Ramos, T.D. Dye, I.D. Fernandez, C.M. Velez Vega, D. Vega Ocasio, E. Avendaño, N.R. Cardona Cordero, C. Di Mare Herring, Z. Quiñones Tavarez, A. Dozier, S. Groth.

23/9:45 Utilization of a post-result follow-up chatbot and family sharing tool among patients receiving clinically actionable exome sequencing results. T. Schmidlen, C. Jones, C. McCormick, E. Vanenkevort, A. Sturm.


Wednesday, October 16

9:00 AM–10:00 AM

Concurrent Platform Session A

14. New Discoveries in Long-studied Genes: Cancer Syndromes

Room 360D, Level 3, Convention Center

Moderators: Alison Klein, Johns Hopkins Univ, Baltimore
  Philip Lupo, Baylor Col Med, Houston

 

24/9:00 Rare germline functional variant in ARHGAP30 gene predisposes to Li-Fraumeni syndrome-like cancers. R. Krahe, J.W. Wong, Y. Deng, L.L. Bachinski, S.E. Olufemi, Q. Chen, J. Hsu, M. Sirito, Y. Wang, K.A. Baggerly, S.T. Arnold, J.E. Ladbury, P. Gang, W. Wang, B.R. Gracia, G.I. Karras, H. Hampel, A. de la Chapelle, P.L. Mai, S.A. Savage, C.L. Snyder, H.T. Lynch, J. Bojadzieva, G. Lozano, L.C. Strong.

25/9:15 Li-Fraumeni syndrome? A multi-tissue NGS strategy to define constitutional TP53 status. J.N. Weitzel, J. Garber, D. Castillo, S. Sand, R. Mejia, A. Cervantes, K.W.K. Tsang, J. Mokhnatkin, J. Wang, X. Wu, J. Herzog, B. Nehoray, T.P. Slavin.

26/9:30 Comprehensive functional classification of Lynch syndrome missense variants. X. Jia, B. Burugula, V. Chen, M. Maksutova, S. Jayakody, J. Kitzman.

27/9:45 Disparate genes with germline pathogenic and likely pathogenic variants converging on p53 network can be etiologic for pediatric/adolescents and young adults solid tumor cancer predisposition. S. Akhavanfard, R. Padmanabhan, L. Yehia, F. Chen, C. Eng.


Wednesday, October 16

9:00 AM–10:00 AM

Concurrent Platform Session A

15. Gene Expression Variation Across Diverse Global Populations

Room 361D, Level 3, Convention Center

Moderators: Jackie MacArthur, European Bioinformatics Inst, Cambridge, UK
  Emily Davenport, Cornell Univ, Ithaca

 

28/9:00 Optimizing gene expression predictive performance across global populations. P. Okoro, R. Schubert, A. Luke, L.R. Dugas, H.E. Wheeler.

29/9:15 Local-ancestry based models for improved gene-expression prediction in African Americans. L. Nahlawi, Y. Zhong, T. De, C. Alacron, M.A. Perera.

30/9:30 Impact of discordant ancestral structure between coding and regulatory regions on gene expression. W.J. Alvarez, S.W. Kong, I.H. Lee.

31/9:45 Cross-population portability and statistical power of predictive models for gene expression. K. Keys, A.C.Y. Mak, M.J. White, W.L. Eckalbar, A.W. Dahl, J. Mefford, A.V. Mikhaylova, M.G. Contreras, J.R. Elhawary, C. Eng, D. Hu, S. Huntsman, S.S. Oh, S. Salazar, M.A. Lenoir, J.C. Ye, T.A. Thornton, N. Zaitlen, E.G. Burchard, C.R. Gignoux.


Wednesday, October 16

9:00 AM–10:00 AM

Concurrent Platform Session A

16. Telomeres: What You Need to Know at the End

Room 370A, Level 3, Convention Center

Moderators: Elizabeth Hauser, Duke Univ, Durham
  Floris Barthel, Jackson Lab Genomic Med, Farmington

 

32/9:00 Determinants of telomere length across human tissues. K. Demanelis, F. Jasmine, L.S. Chen, M. Chernoff, L. Tong, J. Shinkle, M. Sabarinathan, H. Lin, E. Ramirez, M. Oliva, S. Kim-Hellmuth, B.E. Stranger, K. Ardlie, F. Aguet, J. Doherty, H. Ahsan, M.G. Kibriya, B.L. Pierce, Genotype-Tissue Expression (GTEx) Consortium.

33/9:15 Thirteen novel genetic loci identified for telomere length leveraging 75K whole genome sequences in the Trans-Omics for Precision Medicine (TOPMed) Program. M.A. Taub, J. Weinstock, K. Iyer, L.R. Yanek, M.P. Conomos, M. Arvanitis, A.R. Keramati, J. Lane, T. Blackwell, C. Laurie, T. Thornton, A. Battle, J.A. Perry, N. Pankratz, A. Reiner, R.A. Mathias, on behalf of the NHLBI TOPMed Consortium.

34/9:30 Leukocyte telomere length and occurrence of chronic health conditions among survivors of childhood cancer: A report from the St. Jude Lifetime Cohort. N. Song, Z. Li, N. Qin, C.R. Howell, C.L. Wilson, J. Easton, H. Mulder, M.N. Edmonson, M.C. Rusch, J. Zhang, M.M. Hudson, Y. Yasui, L.L. Robison, K.K. Ness, Z. Wang.

35/9:45 The nuclear organization of telomeres as a genomic exploration tool in triple negative breast cancer. O. Samassekou, S. Mai.


Wednesday, October 16

9:00 AM–10:00 AM

Concurrent Platform Session A

17. Causes and Mechanisms Underlying Mendelian Neurogenetic Conditions

Room 371A, Level 3, Convention Center

Moderators: Renske Oegema, Univ Med Cent Utrecht, Netherlands
  Christian Thiel, Friedrich-Alexander Univ, Erlangen, Germany

 

36/9:00 Noncoding CGG repeat expansions as common causative mutations for three diseases, neuronal intranuclear inclusion disease, oculophryngodistal myopathy, and an overlapping disease. H. Ishiura, S. Shibata, J. Yoshimura, Y. Suzuki, W. Qu, K. Doi, M.A. Almansour, J.K. Kikuchi, M. Taira, J. Mitsui, Y. Takahashi, Y. Ichikawa, T. Mano, A. Iwata, Y. Harigaya, M.K. Matsukawa, T. Matsukawa, M. Tanaka, H. Kowa, S. Murayama, Y. Shiio, Y. Saito, S.Y. Lim, A.H. Tan, J. Shimizu, J. Goto, I. Nishino, T. Toda, S. Morishita, S. Tsuji.

37/9:15 De novo EIF2AK1 and EIF2AK2 variants are associated with developmental delay, movement disorders, cerebellar ataxia, leukoencephalopathy, and neurologic decompensation. D. Mao, C. Reuter, M. Ruzhnikov, A. Beck, E. Farrow, L. Emrick, J. Rosenfeld, K. Mackenzie, L. Robak, M. Wheeler, L. Burrage, M. Jain, D. Calame, M. Graf, S. Masters, B. Lee, I. Thiffault, P. Agarwal, J. Bernstein, H. Bellen, H. Chao, Undiagnosed Diseases Network.

38/9:30 De novo truncating TRIM8 mutations cause a novel pediatric neuro-renal syndrome and abrogate protein localization to nuclear bodies. K. Khan, P.L. Weng, A.J. Majmundar, T.Y. Lim, S. Shril, J.A. Martinez-Agosto, N. Mann, Y. Jin, V. Aggarwal, A. Onuchic-Whitford, F. Buerger, J. Musgrove, B.B. Beck, K.M. Riedhammer, M.R. Benz, J. Hoefele, H.L. Rehm, D.G. MacArthur, S. Mane, V. D’Agati, F. Hildebrandt, S. Sanna-Cherchi, E.E. Davis.

39/9:45 Hypomorphic variants in the deubiquitylase OTUD5 cause multiple congenital defects through altered chromatin dynamics. D.B. Beck, A.B. Basar, H. Oda, D.T. Uehara, J. Inazawa, E. Macnamara, P. D'Souza, J. Bodurtha, W. Mu, K. Baranano, T. Kosho, M. Kempers, M. Walkiewicz, R. Wang, C.J. Tifft, I. Aksentijevich, A. Werner, D. Kastner.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

18. Addressing the Genomics Literacy Gap in Society: A Conversation about the How, What, Why, and Impact of Modern Educational Frameworks

Room 370A, Level 3, Convention Center

Moderators: Rivka Glaser, Stevenson Univ, Owings Mills
  Adam Hott, Hudson Alpha Inst Biotech, Huntsville

 

Student: "My grandmother has Alzheimer's, so I have a 50% chance of having it too." Patient: "No one in my family has this, so why should I get tested?" Headline: "Parents May One Day Be Morally Obligated to Edit Their Baby's Genes." How do we know that our energy and time spent in genetics and genomics education are effective? Are we making any difference in the genomic literacy of K-16 students, graduate students, healthcare providers, and the general public? What is standing in the way of the utopian genomically literate populace? As genetics professionals and educators, we recognize the importance of being genomically literate. However, as the pace of genetic and genomic knowledge and technologies increases, gaps in genetic and genomic literacy between genetics professionals and other subsets of the population increases. This session will explore the effectiveness of our genetics and genomics education pipeline. Through both short presentations and a large group panel discussion, this session will foster audience member engagement in a conversation about what is working and what barriers are in the way of a truly genomically literate society.

 

10:30 AM   Introduction.

10:35 AM   Reaching the public to increase community genomic literacy. N. Lamb. HudsonAlpha Inst Biotech, Huntsville.

10:55 AM   Models for teaching and learning about DNA. D. Newman. Rochester Inst Technol.

11:15 AM   Healthcare provider education in genomics. B. Biesecker. Research Triangle Inst, Intl, Washington, D.C.

11:35 AM   Effective undergraduate education for the successful preparation of graduate students. S. McClymont. Johns Hopkins Sch Med, Baltimore.

11:55 AM   Panel discussion.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

19. Beyond the Genome Sequence: Integrating Genes, Enhancers, and Pathways in Development and Disease

Grand Ballroom B, Level 3, Convention Center

Moderators: Sumantra Chatterjee, New York Univ Sch Med
  Tychele N. Turner, Washington Univ Sch Med St Louis

 

Despite progress in cataloging disease-causing genes for various multifactorial disorders, their underlying biology has been difficult to unravel. As large-scale exome and whole-genome sequencing data become available, finding disease-associated variants is becoming easier, but not finding their biological effects. Solving this puzzle will require us to place genes in their correct spatio-temporal context, deciphering their regulatory control and building their gene regulatory networks (GRNs). Building these networks will help us to connect the many coding and non-coding variants by elucidating the highly integrative and interactive properties of the human genome. In this session, we will bring together diverse speakers highlighting the multiple ways of connecting various components of the genome that contribute to a phenotype and disease state. We will discuss work that integrates both computational and experimental approaches to understand how disruption of critical genes and non-coding elements involved in specific processes leads to distinct effects across different cells and tissues. Figuring out these discrete effects will lead to a better understanding of normal developmental processes and the complexities of cellular response in disease. The various talks will demonstrate how comprehension of these networks has an important lesson for systems biology: the whole idea of a system is to provide robustness from variation and mutations, but a well-integrated system can have the opposite effect and lead to disease even when only one primary component is perturbed due to effect amplification through the network.

 

10:30 AM   Transcriptional regulatory networks underpinning Hirschsprung disease. S. Chatterjee. New York Univ Sch Med.

11:00 AM   Highly multiplexed genome engineering methods to pair human regulatory elements with their target genes. M. Gasperini. Univ Washington, Seattle.

11:30 AM   Identification of gene regulatory network components in autism. T.N. Turner. Washington Univ Sch Medicine St Louis.

12:00 PM   Systematic approaches to analysis of regulatory variation. M. Maurano. New York Univ Sch Med.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

20. DNA in the Public Sphere: How Genomic Information is Used and Protected Outside of Research and Medicine

Grand Ballroom C, Level 3, Convention Center

Moderators: Cristina Kapustij, NHGRI/NIH, Bethesda
  Sara Katsanis, Duke Univ, Durham

 

Over the years, genetics has grown from a purely academic discipline to one that revolutionized forensics, genealogy, and medicine. Millions of Americans have gained access to their own personal genomic data, with the consumer genomics market value expected to grow to over $300 million in the next four years. As genomics becomes more accessible in the consumer and legal worlds, it has also become entangled in national conversations about race and ethnicity, family reunification, criminal justice, and data privacy. The use of DNA has moved well beyond the clinical and research context and now plays an important role in forensics, disaster response, and border security. This session will bring together experts from diverse fields who will discuss how genomic data are incorporated in their work in various settings, the policies (or lack thereof) that shape this work, and the difficulties in protecting genetic information used in these settings. It will introduce attendees to the importance and limits of genomic information in forensics (especially with the emergence of forensic genealogy), the challenges of sharing DNA data across borders for the identification of missing migrants, and the policy considerations for employing DNA as a biometric for border security. The closing panel will serve as an open forum for discussion on the strengths and weaknesses of relevant policies, as well as opportunities for new policy development around topics such as genomic privacy, security, confidentiality, and transparency.

 

10:30 AM   Introduction. C. Kapustij. NHGRI/NIH, Bethesda.

10:40 AM   Use of genetic information in criminal and civil litigation. S. Mercer. Raquin Mercer LLC, Rockville.

10:55 AM   Solving cold cases using genetic genealogy. C. Moore. Parabon NanoLabs/DNA Detectives, Reston.

11:10 AM   Long-term dead: Identification of missing migrants at the Texas-Mexico border. K. Spradley. Texas State Univ, San Marcos.

11:25 AM   Government and genetics: Balancing national security and humanitarian interests. J. Wagner. Geisinger Hlth Syst, Danville.

11:40 AM   Synthesis and introduction to panel. S. Katsanis. Duke Univ, Durham.

11:50 AM   Panel discussion.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

21. Emerging Views of Human Brain Evolution and Development from Comparative Neurogenetics

Room 361D, Level 3, Convention Center

Moderators: Armin Raznahan, NIMH, Bethesda
  Jason Stein, Univ North Carolina Chapel Hill

 

The expansion of the human neocortex in anatomically modern humans has, in part, led to our unique cognitive and social abilities. Genome sequencing of our extant relatives, archaic humans, and current human populations has identified loci undergoing selection along the human lineage. However, the specific genetic changes leading to cortical expansion are very poorly understood. Because neuropsychiatric disorders impact cognitive and behavioral domains that are uniquely developed in humans, comparative neurogenetics may also provide fundamental insights into the biology of risk for neuropsychiatric disorders. Functional analyses, described in this session, allow us to annotate the effects of genetic variants under selection on human brain structure, function, and development. Nadav Ahituv will present the functional impact of fixed changes within human accelerated regions of the genome in human and chimpanzee iPSC-derived neural progenitor cells. Amanda Tilot will present a large-scale assessment of how Neanderthal introgression continues to influence a neuroimaging-derived brain-shape phenotype that reflects a uniquely human neurodevelopmental process. Jason Stein will present a series of studies that determine the functional impact of selected alleles on cortical structure using GWAS of cortical structure via MRI. Armin Raznahan will present work that combines in vivo neuroimaging and postmortem transcriptomic maps of the human brain to identify candidate mediators of regional cortical expansion in humans and the role of these expanded systems in neurodevelopmental disorders. Collectively, these presentations will showcase the rapid understanding of genetic variants impacting brain structure and development across human evolution in the burgeoning field of comparative neurogenetics.

 

10:30 AM   Massively parallel dissection of human accelerated regions. N. Ahituv. UCSF.

11:00 AM   Neandertal introgression sheds light on modern human endocranial globularity. A. Tilot. Max Planck Inst Psycholinguistics, Nijmegen, Netherlands.

11:30 AM   Unearthing the evolutionary history of common genetic variants influencing human cortical surface area. J. Stein. Univ North Carolina Chapel Hill.

12:00 PM   Transcriptional decoding of size-dependent brain shape diversity in humans. A. Raznahan. NIMH, Bethesda.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

22. Functional Validation of Rare Variants Using Physiologically Relevant Experimental Systems

Grand Ballroom A, Level 3, Convention Center

Moderators: Daniel C. Koboldt, Nationwide Children's Hosp, Columbus
  Anne O'Donnell-Luria, Boston Children's Hosp

 

Functional validation of genomic variants associated with disease is a vital yet increasingly difficult task in the face of rapidly accelerated genomic discovery. Crucially, it is now far easier and more cost-effective to identify candidate disease-causing variants than it is to determine their biological consequences and mechanisms of pathogenesis. Fortunately, numerous experimental tools and approaches have emerged to investigate the impact of rare variants at a molecular level. Here, we highlight the use of scalable model systems that employ cutting-edge molecular toolkits to interpret human genetic lesions. These include coding and non-coding changes as well as point mutations or copy number variants. Our session features experts in diverse model systems, but the speakers are unified by a common goal of interpreting variation found in humans. Attendees will learn how: (1) CRISPR-enabled enhancer reporter assays have enabled testing thousands of candidate enhancer variants in mice; (2) Zebrafish assays have facilitated gene discovery and copy number variant dissection in rare pediatric syndromes; (3) three-dimensional organoids grown from patient iPS cells make it possible to assess the impact of genomic variants on brain structure and physiology; and (4) Drosophila models offer a tractable means to accelerate both gene discovery and therapeutic development in undiagnosed disorders. In summary, our session will demonstrate how elegant biological approaches can address the major challenges of interpretation and serve as a necessary complement to in silico predictions for the human genetics community.

 

10:30 AM   Linking enhancer variation to human disease in vivo. L. Pennacchio. Lawrence Berkeley Natl Lab.

11:00 AM   Modeling pediatric genetic disease in the developing Zebrafish. E. Davis. Duke Univ Med Ctr, Durham.

11:30 AM   Using brain organoids to investigate rare genomic variants in human neurological disorders. M. Hester. Nationwide Children's Hosp, Columbus.

12:00 PM   Using Drosophila to study new disease associated rare human variants and mechanisms. H. Bellen. Texas Children's Hosp, Houston.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

23. Clinical Spotlight: Novel Insights into the Genetics of Reproduction: Precision Medicine and Personalized Assisted Reproductive Technologies

Room 310A, Level 3, Convention Center

Moderators: Rima Slim, McGill Univ Hlth Ctr Res Inst, Montreal, Canada
  Lei Wang, Fudan Univ, Shanghai, China

 

Little data is known about the genetic bases of recurrent reproductive loss and infertility mainly due to their genetic heterogeneity. In fact, the genetics of reproductive loss and infertility has a lot of delays relative to other medical disciplines such as neurology, biochemistry, ophthalmology, and pediatrics. The advent of next-generation sequencing (NGS) in the last decade has opened an unprecedented opportunity to tackle genetically heterogeneous conditions and allowed the recent identification of several genes responsible for infertility and reproductive loss in humans. This session will address the genetic bases of female and male reproductive failure and show the impact of NGS on the identification of several of their responsible genes. The first speaker, Aleksandar Rajkovic, will describe his work on gonadal development, germ cell differentiation, and folliculogenesis. He will show how germ cell-specific transcriptional regulators determine the pool of primordial follicles, their activation, reproductive life span, and how their mutations lead to premature ovarian failure. The second speaker, Lei Wang, will talk about the genetic basis of female infertility. He will describe his work on the identification of novel Mendelian phenotypes and genes responsible for abnormalities in oocyte maturation, fertilization, and early embryonic development. The third speaker, Rima Slim, will present her work on a particular form of pregnancy loss, called molar pregnancy. She will describe current knowledge about four causative genes for recurrent moles, their roles in its pathogenesis, and link to recurrent miscarriages and female and male infertility. The fourth speaker, Pierre Ray, will focus on the genetics of male infertility and his identification of several genes responsible for abnormalities in spermatogenesis. The four speakers will end their talks with lists of genes that need to be tested in patients and criteria of patients’ inclusion. The session assembles top experts in their fields, from four different countries, who will bring different academic and medical perspectives since the four countries are under different health care systems and regulations.

 

10:30 AM   Genetic bases of premature ovarian failure. A. Rajkovic. UCSF.

11:00 AM   Missing Mendelian phenotypes in genetic abnormalities of oocyte maturation, fertilization, and embryonic development. L. Wang. Fudan Univ, Shanghai, China.

11:30 AM   Genetic bases and mechanisms of recurrent molar pregnancies. R. Slim. McGill Univ Hlth Ctr Res Inst, Montreal, Canada.

12:00 PM   High-throughput sequencing reveals that a large number of genes is involved in human male infertility. P. Ray. Univ Grenoble Alpes, France.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

24. Recent Progress on Identity-by-Descent

Room 360D, Level 3, Convention Center

Moderators: Degui Zhi, Univ Texas Hlth Sci Cen Houston
  Xiaoming Liu, Univ South Florida, Tampa

 

Identity-by-Descent (IBD) segments are fundamental genetic concepts and relevant to many aspects of human genetics. While traditionally IBD studies were mostly theoretical studies and on small samples, they have recently become more data-driven thanks to the availability of large cohorts with genotypes and new computational methods. In particular, modern IBD methods have begun to offer new insights into genetic genealogy, recent population history, and disease risks due to rare variants and haplotypes. This session will showcase cutting-edge analytical methods and the new results brought by these methods. A short introduction will be followed by four talks. David Balding will offer insights into theoretical frameworks for IBD and relatedness and applications in association analysis and heritability. Sharon Browning will discuss inference of population history from IBD segments. Ardalan Naseri will review recent efficient methods for identifying IBD segments from very large genotyped samples. Eurie Hong will describe a large collection of genotyped cohorts available at a direct-to-consumer company, their findings, and the implications for society.

 

10:30 AM   Kinship: Theory and practice in genome-wide analyses. D. Balding. Univ Melbourne, Australia.

11:00 AM   Inferring the past thousand years of demographic history using segments of identity by descent. S. Browning. Univ Washington, Seattle.

11:30 AM   Efficient computational methods for identifying IBD segments from biobanks. A. Naseri. Univ Texas Hlth Sci Cent Houston.

12:00 PM   Pedigrees and genealogical records provide a historical portrait of population structure. E. Hong. AncestryDNA LLC, San Francisco.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

25. Value Assessment of Genomic Testing from Diverse Stakeholder Perspectives in Health Services

Room 371A, Level 3, Convention Center

Moderators: Scott J. Spencer, Univ Washington, Seattle
  Christine Lu, Harvard Univ, Boston

 

We continue to see increased availability of both next-generation sequencing and additional biomedical data. Despite the growth of these resources, we have not seen the sweeping improvements in health that some anticipated. This is due to a variety of challenges related to the translation of genome sciences into clinical care and practice at the patient, provider, health systems, and payer levels for genetic testing. To address several translational challenges, it is critical to (1) understand the evolving marketplace and test quality, (2) understand how genomic information influences how patients and providers pursue healthcare services, (3) apply health economic methods to assess the value utilizing genomic information, and (4) identify strategies and methods for evaluation of genetic tests and tools from various stakeholder perspectives. Considering these challenges, Gillian Hooker will introduce the genetic testing marketplace and discuss attributes associated with test value. Next, Ragan Hart will discuss decision analysis for discerning cost-effectiveness of next-generation sequencing tests, highlight limitations of current value assessment methods, and report on proposed solutions. Additionally, Kurt Christensen will discuss approaches to conducting economic evaluations alongside clinical studies. Finally, Erick Lin will discuss an evidence review process for assessing value associated with diagnostic tests. The presentations will be followed by a panel discussion with all of the speakers. This session intends to offer insights from various experts who are developing and applying solutions as they relate to these questions and how to best utilize genetic data and health data for translational impact in clinical practice.

 

10:30 AM   Clinical genetic testing in the genome era: A view across the U.S. landscape of value, quality, and reimbursement. G. Hooker. Concert Genet, Franklin.

10:50 AM   Decreasing uncertainty within the value assessment process for genomic testing. R. Hart. Stanford Univ.

11:10 AM   Evaluating the economic impact of genomic testing during clinical trials. K. Christensen. Brigham & Women's Hosp, Boston.

11:30 AM   Industry evidence review framework for evaluating diagnostic tests. E. Lin. Blue Cross Blue Shield Assn, Chicago.

11:50 AM   Panel discussion.


Wednesday, October 16

10:30 AM–12:30 PM

Concurrent Invited Session II

26. What about the Phenotype? Integrating Electronic Health Records to Drive Discovery in Precision Health

Hall B, Level 1, Convention Center

Moderators: Anna O. Basile, New York Genome Ctr
  Molly A. Hall, Pennsylvania State Univ, University Park

 

Copious amounts of rich, diverse clinical data have become increasingly available for research through electronic health record (EHR) databanks and clinical repositories. EHRs provide a dense source of longitudinal data that can be integrated for research tasks such as cohort development, outcome ascertainment, and clinical translation. EHR-coupled biorepositories combined with advancements in machine learning approaches and natural language processing provide a unique opportunity for studying the complex architecture of health and disease by using the biomedical products of clinical care. This session will focus on the ways that EHR-extracted data can be leveraged in driving discovery in precision health and genomics. Applications include developing refined phenotype algorithms, elucidating patterns for the purpose of homogeneous patient stratification, using phenome-wide association studies (PheWAS) to find novel relationships among diseases, discovering phenotype-genotype associations, evaluating drug usage, identifying potential drug interactions, and uncovering pleiotropic relationships. This session will also tackle efficient research strategies needed to address challenges and limitations associated with EHR-derived data and analyses including the handling of heterogeneous, multivariate and highly dimensional data, addressing missing attributes, and the computational feasibility of analytic approaches. Overall, the EHR provides an invaluable resource of information that can be leveraged to build accurate predictive models that will aid in uncovering the genetic basis of common diseases as well as potentially advancing diagnosis, treatment, and prevention of disease.

 

10:30 AM   Genotyping to inform phenotyping in electronic health records. D.C. Crawford. Case Western Reserve Univ, Cleveland.

11:00 AM   Human-disease phenotype map derived from an EHR-linked biobank. D. Kim. Univ Pennsylvania, Philadelphia.

11:30 AM   Exploring the phenome and the relationship with the genome using EHR-linked biobanks. M.D. Ritchie. Univ Pennsylvania, Philadelphia.

12:00 PM   Latent phenotype models to improve genetic analyses in incomplete medical records. N.P. Tatonetti. Columbia Univ, New York.


Wednesday, October 16

1:00 PM–2:00 PM

Platform Session

112. Exome and RNA-based Sequencing Methods for Variant Interpretation to Improve Clinical Utility

Room 310A, Level 3, Convention Center

Moderator: Reha Toydemir, Univ Utah, Salt Lake City

 

2609/1:00 Outcomes for reanalysis of exome sequencing data in a large cohort. M. Guillen Sacoto, A. Begtrup, R. Willaert, A. Crunk, E. Heise, L. Rhodes, C. Kucera, L. Havens, J. Juusola.

197/1:15 High-throughput RNA splicing profile increases detection of clinically-actionable variants while reducing inconclusive results in patients with hereditary cancer predisposition. T. Landrith, B. Li, A. Cass, B.R. Conner, S. Wu, H. Vuong, S. Charpentier, J. Burdette, H. LaDuca, T. Pesaran, J. Rae-Radecki Crandall, H. Lu, B. Tippin-Davis, A. Elliot, R. Karam.

2536/1:30 Improving diagnostic yield in clinical and acute care genomics: Rapid PCR studies of splicing variants in tissue-specific genes using blood or fibroblast mRNA. A. Bournazos, L.G. Riley, L.S. Akesson, N.L. Baker, K. Boggs, N. Brown, M. Buckley, M.R. Davis, M. Edwards, L.J. Ewans, A. Fennell, M. Field, M.L. Freckmann, H. Goel, S. Goh, L. Goodwin, K. Kumar, S. Lunke, A. Ma, H. McCarthy, M.P. Menezes, D. Mowat, S.A. Sandaradura, Z. Stark, C. Sue, T.Y. Tan, E. Tantsis, M. Tchan, S.M. White, M. Wilson, D.C. Wright, K. Jones, B. Bennetts, S.T. Cooper.

225/1:45 Reclassification of splicing VUS in neurological disease genes via RNA-seq. S. Ichikawa, B.R. Conner, S. Wu, R. Karam.


Wednesday, October 16

4:15 PM–5:45 PM

Concurrent Platform Session B

27. Precision Medicine: Models and Complex Disease

Hall B, Level 1, Convention Center

Moderators: Conor McClenaghan, Washington Univ St. Louis
  Ashleigh Schaffer, Case Western Reserve, Cleveland

 

40/4:15 Quantifying the polygenic contribution to variable expressivity in eleven rare genetic disorders. M.T. Oetjens, M.A. Kelly, A.C. Strum, R.G.C. Regeneron Genetics Center, C.L. Martin, D.H. Ledbetter.

41/4:30 Aberrant post-translational modifications (PTM) characterize the hepatic proteome of methylmalonic acidemia (MMA). P. Head, I. Manoli, Y. Chen, M. Gucek, C. Venditti.

42/4:45 Targeting transforming growth factor-β (TGFβ) signaling for osteogenesis imperfecta treatment. I. Song, S. Nagamani, D. Nguyen, I. Grafe, E. Munivez, M. Jiang, P. Esposito, J. Goodwin, E. Strudthoff, S. McGuire, V. Shenava, S. Rosenfeld, B. Lee, Brittle Bone Disorders Consortium.

43/5:00 Nonhuman primate models of rare diseases support the development of precision medicine, pharmacogenomics, and gene therapy approaches. S.M. Peterson, B.N. Bimber, L.M. Colgin, A.L. Johnson, A.D. Lewis, B. Ferguson.

44/5:15 An interventional clinical trial to evaluate the role of elamipretide in individuals with Barth syndrome. H.J. Vernon, W.R. Thompson, R. Manuel, A. Aiudi, J.J. Jones, J. Carr, B. Hornby.

45/5:30 Moving human genetics into the mouse: Full human gene-replacement models. M. Koob, K. Karanjeet, K. Benzow.


Wednesday, October 16

4:15 PM–5:45 PM

Concurrent Platform Session B

28. Spectrum of Genomic Alterations in Cancer

Grand Ballroom A, Level 3, Convention Center

Moderators: Georgia Chenevix-Trench, QIMR Berghofer, Brisbane, Australia
  Candace Middlebrooks, NHGRI, Baltimore

 

46/4:15 Gene mapping in breast cancer extended pedigrees using PAM50 tumor dimensions. J. Gardner, M. Madsen, S. Knight, M. Cessna, R. Factor, C. Sweeney, B. Caan, L. Kushi, P. Bernard, N. Camp.

47/4:30 A 585bp structural variant in CTRB2 underlies a pancreatic cancer GWAS risk signal at chr16q23.1. A. Jermusyk, J. Zhong, N. Gordon, I. Collins, E. Abdolalizadeh, S. Parera, T. Zhang, J. Hoskins, K. Connelly, D. Eiser, R. Stolzenberg-Solomon, B. Wolpin, S. Chanock, G. Petersen, J. Shi, C. Westlake, L. Amundadottir, PanScan, PanC4.

48/4:45 Variable expression quantitative trait loci analysis of breast cancer risk variants. G. Wiggins, J. Pearson, M. Black, A. Dunbier, T. Merriman, L. Walker.

49/5:00 Oncogenes co-opt endogenous and ectopic enhancers on extrachromosomal DNA amplifications. A.R. Morton, N. Dogan-Artun, G. MacLeod, C.F. Bartels, M.S. Piazza, S.C. Mack, X. Wang, R.C. Gimple, Q. Wu, Z.J. Faber, B.P. Rubin, S. Shetty, S. Angers, P.B. Dirks, M. Lupien, J.N. Rich, P.C. Scacheri.

50/5:15 Epigenomic translocation of H3K4me3 broad domain: A mechanism of super-enhancer hijacking following oncogenic translocations. A. Mikulasova, K. Fung, N. Karataraki, B.A. Walker, G.J. Morgan, C. Ashby, A. Corcoran, S. Hambleton, D. Rico, L.J. Russell.

51/5:30 Somatic mutations in HLA-class I genes: Associations with tumor burden and HLA homozygosity. M. Dean, M. Viard, M. Yeager, V. Naranbhai, M. Carrington.


Wednesday, October 16

4:15 PM–5:45 PM

Concurrent Platform Session B

29. Single Cell Transcriptomics of the Brain to Inform the Genetics of Neurological Disorders

Grand Ballroom B, Level 3, Convention Center

Moderators: Paivi Pajukanta, David Geffen Sch Med UCLA
  Hae Kyung Im, Univ Chicago

 

52/4:15 Single-cell dissection of brain circuitry across 800+ individuals including AD, schizophrenia, bipolar, ALS, HD, and controls. M. Kellis, J. Davila-Velderrain, S. Mohammadi, Y.P. Park, L. He, C. Boix, M. Kousi, J. Mantero, K. Galani, L.-L. Ho, H. Mathys, J. Young, D.A. Bennett, L.-H. Tsai.

53/4:30 Integrated analysis of rare variants and single-cell expression data provides insights into schizophrenia risk. T. Nguyen, A. Charney, X. He, K. Kendler, P. Sullivan, S. Bacanu, B. Riley, E. Stahl.

54/4:45 Human single-cell transcriptomes identify cell-types and states relevant to brain disorders. S. Gerges, T. Singh, M. Goldman, S. Berretta, S. McCarroll, M. Daly.

55/5:00 Regional heterogeneity in gene expression, regulation, and coherence in the frontal cortex and hippocampus across development and schizophrenia. L. Collado Torres, E.E. Burke, A. Peterson, J.H. Shin, R.E. Straub, A. Rajpurohit, S.A. Semick, W.S. Ulrich, A.J. Price, C. Valencia, R. Tao, A. Deep-Soboslay, T.M. Hyde, J.E. Kleinman, D.R. Weinberger, A.E. Jaffe, BrainSeq Consortium.

56/5:15 Single-cell RNA-sequencing reveals cell-type-specific levels of aneuploidy in mammalian nervous system. T. Li, J. Zhu, R. Li.

57/5:30 Single-cell isoform RNA sequencing characterizes isoforms in thousands of cerebellar cells. H. Tilgner.


Wednesday, October 16

4:15 PM–5:45 PM

Concurrent Platform Session B

30. Analyses Utilizing Biobanks

Grand Ballroom C, Level 3, Convention Center

Moderators: Anne Justice, Geisinger Hlth Syst, Danville
  Adam Locke, Washington Univ St. Louis

 

58/4:15 Global Biobank Meta-analysis Initiative: Powering genetic discovery across human diseases. W. Zhou, B.M. Neale, M.J. Daly, on behalf of Global Biobank Meta-analysis Initiative.

59/4:30 Biclustering of a large gene to phenome catalog of associations unveils hidden connections between complex traits and genes. M. Pividori, A. Barbeira, H. Im.

60/4:45 Multi-trait genome-wide analyses of the brain imaging phenotypes in UK Biobank. C. Wu.

61/5:00 Evaluating the age-of-onset-dependent genetic architecture of complex disorders in the UK Biobank. Y.-C.A. Feng, T. Ge, C.-Y. Chen, J. Smoller, B. Neale.

62/5:15 Exome-by-phenome-wide gene-burden association analyses using electronic health record phenotypes. J. Park, S.M. Damrauer, J. Chen, M.D. Ritchie, D.J. Rader, Regeneron Genetics Center.

63/5:30 Trans-ethnic mega-biobank polygenic risk score analysis involving 676,000 individuals identified blood pressure and obesity as causal drivers affecting human longevity. S. Sakaue, M. Kanai, J. Karjalainen, M. Akiyama, M. Kurki, N. Matoba, A. Takahashi, M. Hirata, M. Kubo, K. Matsuda, Y. Murakami, M. Daly, Y. Kamatani, Y. Okada, FinnGen Project.


Wednesday, October 16

4:15 PM–5:45 PM

Concurrent Platform Session B

31. Genetics and Functional Insights into Cardiovascular Disease

Room 310A, Level 3, Convention Center

Moderators: Julio D. Duarte, Univ Florida, Gainesville
  Ana Vinuela, Univ Geneva, Switzerland

 

64/4:15 Large-scale genome-wide association studies identify novel susceptibility loci for myocardial infarction. J.A. Hartiala, Y. Han, Q. Jia, Z. Kurt, P. Huang, N.C. Woodward, J. Gukasyan, D.A. Trégouët, N.L. Smith, M. Seldin, C. Pan, M. Mehrabian, A.J. Lusis, P. Bazeley, A.A. Quyyumi, M. Scholz, J. Thiery, W. März, L.J. Howe, F.W. Asselbergs, R.S. Patel, L.P. Lyytikäinen, M. Kähönen, T. Lehtimäki, T.V.M. Nieminen, J.O. .Laurikka, X. Yang, W.H.W. Tang, S.L. Hazen, H. Allayee, The GENIUS-CHD Consortium.

65/4:30 Whole genome sequencing association analysis of stroke and its subtypes in a multi-ethnic population from Trans-Omics for Precision Medicine (TOPMed). Y. Hu, J. Haessler, P. Auer, K. Wiggins, A. Moscati, A. Beiser, N. Heard-Costa, L. Raffield, J. Chung, S. Marini, C. Anderson, J. Rosand, H. Xu, L. Lange, A. Correa, S. Seshadri, S. Rich, R. Do, R. Loos, J. Bis, T. Assimes, B. Silver, S. Liu, R. Jackson, S. Smoller, B. Mitchell, M. Fornage, A. Reiner, C. Kooperberg, the TOPMed Stroke Working Group.

66/4:45 Genetic studies in the eMERGE network and UK Biobank offer new insights into pleiotropy across cardiovascular diseases and central nervous system disorders. X. Zhang, Y. Veturi, A. Verma, T.G. Drivas, W.K. Chung, D. Crosslin, J.C. Denny, D. Fasel, H. Hakonarson, S. Hebbring, G.P. Jarvik, I. Kullo, E.B. Larson, S.A. Pendergrass, L. Rasmussen-Torvik, D. Schaid, P. Sleiman, J.W. Smoller, I.B. Stanaway, W. Wei, C. Weng, M.D. Ritchie.

67/5:00 Gene expression and genetic variation of ERG is associated with inflammation in endothelial cells and risk of coronary artery disease in humans. J. Gukasyan, Q. Jia, N. Woodward, R. Zhu, Y. Han, L.K. Stolze, Z. Kurt, X. Yang, C.E. Romanoski, J.A. Hartiala, H. Allayee.

68/5:15 Investigating the mechanisms underlying genetic risk for coronary artery disease utilizing endothelial cells. L. Stolze, M. Whalen, A. Conklin, A. Solomon, M. Kaikkonen-Määttä, C. Romanoski.

69/5:30 Prioritization of genomic loci for coronary artery disease using targeted CRISPR screens for endothelial dysfunction. F. Wuennemann, T. Fotsing Tadjo, M. Beaudoin, K.S. Lo, G. Lettre.


Wednesday, October 16

4:15 PM–5:45 PM

Concurrent Platform Session B

32. Taking a Closer Look: New Discoveries in Mendelian Eye Diseases

Room 360D, Level 3, Convention Center

Moderators: Anne Slavotinek, UCSF
  Gabrielle Lemire, Children's Hosp Eastern Ontario, Ottawa, Canada

 

70/4:15 Ceramide synthase TLCD3B as a novel gene associated with human recessive cone-rod dystrophy. R.E. Bertrand, K.H. Xiong, C. Thangavel, J. Wang, R. Ba-Abbad, R.T. SimÕes, K.J. Carss, F.L. Raymond, K. Wang, Y. Li, F.B.O. Porto, A.R. Webster, G. Arno, R. Chen.

71/4:30 SSBP1 mutations cause a complex optic atrophy spectrum disorder with mitochondrial DNA depletion. F. Ullah, D. Dotto, I. Meo, P. Magini, M. Gusic, A. Maresca, L. Caporali, F. Palombo, F. Tagliavini, E. Baugh, B. Macao, Z. Szilagyi, C. Peron, M. Gustafson, C. Morgia, P. Barboni, M. Carbonelli, M. Valentino, R. Liguori, V. Shashi, J. Sullivan, S. Nagaraj, E. Davis, M. Seri, M. Falkenberg, H. Prokisch, N. Katsanis, V. Tiranti, T. Pippucci, V. Carelli.

72/4:45 Identification of de novo missense variants in WDR37 as a novel cause of human disease: Delineation of the phenotype and functional studies. L. Reis, E. Sorokina, S. Thompson, S. Muheisen, M. Velinov, C. Zamora, A. Aylsworth, E. Semina.

73/5:00 De novo variants in WDR37 are associated with epilepsy, colobomas, dysmorphism, developmental delay, intellectual disability, and cerebellar hypoplasia. O. Kanca, J.C. Andrews, P.T. Lee, C. Patel, S. Braddock, A.M. Slavotinek, J.S. Cohen, C.S. Gubbels, K.A. Aldinger, J. Williams, M. Indaram, A. Fatemi, T.W. Yu, P.B. Agrawal, G. Vezina, B. Gangaram, J. Wynn, R. Hernan, G. Mychaliska, W.K. Chung, T.C. Markello, W.B. Dobyns, D.R. Adams, W.A. Gahl, M.F. Wangler, S. Yamamoto, H.J. Bellen, M.C.V. Malicdan, Undiagnosed Disease Network.

74/5:15 Biallelic VPS35L pathogenic variants cause 3C/Ritscher-Schinzel-like syndrome through dysfunction of retriever complex. K. Kato, Y. Oka, H. Muramatsu, F. Vasilev, T. Otomo, H. Oishi, Y. Kawano, Y. Nakazawa, T. Ogi, Y. Takahashi, S. Saitoh.

75/5:30 Identification of 46 novel recessive candidate genes for intellectual disability and visual impairment in 350 consanguineous families. S.E. Antonarakis, S.A. Paracha, S. Imtiaz, A. Nazir, Y.M. Waryah, P. Makrythanasis, S. Qureshi, S. Saeed, J. Khan, E. Falconnet, M. Guipponi, C. Borel, M.A. Ansari, Z. Iqbal, E. Frengen, E. Ranza, F.A. Santoni, K. Gul, J. Ahmed, M.T. Sarwar, A.M. Waryah, M. Ansar.


Wednesday, October 16

4:15 PM–5:45 PM

Concurrent Platform Session B

33. Improved Structural Variation Detection Leads to New Insights into Disease and Development

Room 361D, Level 3, Convention Center

Moderators: Ryan Mills, Univ Michigan Med Sch, Ann Arbor
  Christopher Grochowski, Baylor Col Med, Houston

 

76/4:15 Analyses of 1,268 breakpoints from balanced chromosomal abnormalities reveals patterns of three-dimensional reorganization associated with human developmental anomalies. C. Lowther, M.M. Mehrjouy, M. Bak, R.L. Collins, H. Brand, B.B. Currall, K. O'Keefe, Z. Dong, K.W. Choy, E.S. Wilch, O.A. Clark, T. Kammin, S.L.P. Schilit, M.B. Rasmussen, A.S.C. Fonseca, T. Varilo, J.F. Mazzeu, K.T. Abe, A. Lindstrand, C. Sismani, K. Õunap, C. Schluth-Bolard, S. Temel, E.C. Liao, C.C. Morton, J.F. Gusella, P. Jacky, I. Bache, N. Tommerup, M.E. Talkowski, Developmental Genome Anatomy Project (DGAP), International Breakpoint Mapping Consortium (IBMC).

77/4:30 Long read single molecule sequencing identifies putative fetal hemoglobin modifier loci in Africans with sickle cell anemia. P. Lurie, B. Tayo, G. Ayodo, S. Obaro, T. Akingbola, N. Hall, R. Harris, B. Henn, S. Gopalan, Q. Meng, S. Jhangiani, R. Cooper, G. Lettre, K. Worley, A. Wonkman, F. Sedlazeck, N. Hanchard.

78/4:45 DeBreak: Deciphering the exact breakpoints of structural variants using long sequencing reads. Z. Chong, Y. Chen.

79/5:00 Application of long read genome sequencing to patients with undiagnosed diseases. C.M. Reuter, A.N. Raja, D.B. Zastrow, R. Ungar, J.N. Kohler, D.E. Bonner, S. Sutton, L. Fernandez, M. Majcherska, C. McCormack, S. Marwaha, S. Utiramerur, N.I.H. Undiagnosed Diseases Network, P.G. Fisher, J.A. Bernstein, E.A. Ashley, M.T. Wheeler.

80/5:15 Integration of optical genome mapping and sequencing technologies for identification of structural variants in disorders/differences of sex development (DSD). E. Vilain, S. Bhattacharya, M. Almalvez, E.C. Delot, H. Barseghyan.

81/5:30 Developmental genome anatomy project (DGAP): Are there important clinical insights still to be learned from classical cytogenetics? R. Pina-Aguilar, O. Altiok-Clark, B.B. Currall, C. Lowther, K. Nalbandian, J.F. Gusella, E. Liao, M.E. Talkowski, C.C. Morton.


Wednesday, October 16

4:15 PM–5:45 PM

Concurrent Platform Session B

34. Fine-scale Population Structure in Asia and America

Room 370A, Level 3, Convention Center

Moderators: Ellen Quillen, Wake Forest Sch Med, Winston Salem
  Pedro Orozco del Pino, Univ Michigan, Ann Arbor

 

82/4:15 The genomic formation of human populations in Central and South Asia. V. Narasimhan, N. Patterson, D. Reich, on behalf of the Central and South Asia Ancient DNA Study.

83/4:30 The fine-scale genetic structure of the Han Chinese population and a reference panel of 100K individuals for genotype imputation and association studies. X. Wang, C. Liu, X. Ma, Y. Gao, X. Zhang, Y. Pan, C. Zhang, Y. Wang, S. Xu.

84/4:45 Recent population history inferred from more than 5,000 high-coverage South Asian genomes. J. Wall, J. Robinson, S. Belsare, A. Bhaskar, R. Gupta, J. Tom, T. Bhangale, R.K. Rai, A. Butterworth, J. Danesh, V. Mohan, A. Ghosh, A. Barik, A. Chowdhury, D. Saleheen, S. Kathiresan, E. Stawiski, A. Peterson.

85/5:00 Fine-scale population structure and demographic history of British Pakistanis and its implications for disease risk. E. Arciero, T. Tsismentzoglou, D. Mason, N. Small, E. Sheridan, R. Trembath, M.E. Hurles, D.A. van Heel, J. Wright, M. Iles, H.C. Martin.

86/5:15 Identity-by-descent mapping of 87,131 genomes reveals the structure and recent genealogical history of Han Chinese populations. A. Lan, X. Yao, S. Tang, L. Wang, K. Kang, H. Weng, X. Wu, G. Chen.

87/5:30 A paleogenomic reconstruction of the deep population history of Central and South America. N. Nakatsuka, C. Posth, I. Lazaridis, C. Barbieri, P. Skoglund, T. Lamnidis, S. Mallick, N. Rohland, J. Sandoval, R. Burger, E. Tomasto-Cagigao, C. Méndez, G. Politis, G. Valverde, A. Cooper, B. Llamas, W. Haak, D. Kennett, A. Strauss, J. Krause, D. Reich, L. Fehren-Schmitz.


Wednesday, October 16

4:15 PM–5:45 PM

Concurrent Platform Session B

35. Statistical Methods for GWAS Interpretation with Gene Expression Data

Room 371A, Level 3, Convention Center

Moderators: Jonathan Pritchard, Stanford Univ
  Hilary Finucane, Broad Inst, Boston

 

88/4:15 Network centrality measures of colocalized genes and phenotypes in UK Biobank and 48 tissues from the Genotype-Tissue Expression Project. G. Rocheleau, A. Dobbyn, E. Stahl, H.-H. Won, R. Do.

89/4:30 Leveraging gene co-expression pattern to infer trait-relevant tissues in genome-wide association studies. L. Shang, X. Zhou.

90/4:45 Calculating principled gene priors for genetic association analysis. L. Thakur, J. Flannick.

91/5:00 Transcriptomic-LD-score regression (tLDSC). C. Chatzinakos, N.G. Harnett, B.C. Bowlby, L.D. Nickerson, K.J. Ressler, S.A. Bacanu, N.P. Daskalakis.

92/5:15 A powerful statistical framework to leverage tissue-specific gene expression regulation in identifying complex disease-associated genes. W. Liu, M. Li, W. Zhang, G. Zhou, J. Wang, X. Wu, H. Zhao.

93/5:30 Ensemble of colocalization methods improves causal gene prioritization in simulations and GWAS. M.J. Gloudemans, A.S. Rao, B. Liu, B. Balliu, D. Calderon, J.K. Pritchard, E. Ingelsson, S.B. Montgomery.


Wednesday, October 16

6:00 PM–6:15 PM

36. ASHG Victor A. McKusick Leadership Award Presentation and Lecture: The Wonders of Genetics: When Rare Diseases Shed Light on the Common

Hall B, Level 1, Convention Center

Introduction: David L. Nelson, PhD, Baylor College of Medicine

Motivated by the experience of patients, Huda Zoghbi, MD, and her lab at Baylor College of Medicine have studied rare disorders since 1988. Dr. Zoghbi's accomplishments range from discovering genes to identifying their mechanisms and studying potential therapies. Her work demonstrates the value of genetics and genomics research across the spectrum.

Recipient

Huda Zoghbi, MD, DSc
Huda Zoghbi, MD, DSc, Baylor College of Medicine

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.

 


Wednesday, October 16

6:15 PM–6:30 PM

37. ASHG Curt Stern Award Presentation and Lecture: Understanding African Genomic History to Learn About Human Origins and Disease

Hall B, Level 1, Convention Center

Introduction: Neil Risch, PhD, UCSF

Charles Rotimi, PhD, is a genetic epidemiologist who has conducted innovative research to understand the genomic, social, and cultural determinants of metabolic diseases with implications for health disparities. His lab has discovered African-specific variants for diabetes, obesity, lipids, and metabolic syndrome.

Recipients

Charles Rotimi, PhD
Charles Rotimi, PhD, NHGRI

Sarah Tishkoff, PhD, is an anthropologist and population geneticist whose work focuses on the history and evolution of African populations, illustrating Africa’s vital importance in understanding human existence. Dr. Tishkoff and her research team work on identifying genetic and environmental factors that influence both normal variable traits and disease risk in Africans.

Recipient

Sarah Tishkoff, PhD
Sarah Tishkoff, PhD, University of Pennsylvania

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

 


Wednesday, October 16

6:30 PM–6:35 PM

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

Hall B, Level 1, Convention Center

Presented by Fowzan Alkuraya, MD, Awards Committee Chair

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 2019 Annual Meeting. This year’s 6 winners will be announced.

 


Wednesday, October 16

6:35 PM–7:15 PM

39. Featured Plenary Abstract Session II

Hall B, Level 1, Convention Center

Moderators: Beth A. Sullivan, ASHG 2019 Program Committee
  Eric Mendenhall, ASHG 2019 Program Committee

 

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

 

94/6:35 Determining genome-wide significance thresholds in biobanks with thousands of phenotypes: A case study using the Michigan Genomics Initiative. A. Annis, A. Pandit, E. Schmidt, L. Fritsche, P. VandeHaar, C. Brummett, S. Kheterpal, V. Blanc, E. Kaleba, M. Boehnke, S. Zöllner, M. Zawistowski, G. Abecasis.

95/6:55 A survey of epigenetic variation in >23,000 individuals identifies many disease-relevant epimutations and novel CGG expansions. A.J. Sharp, P. Garg, B. Jadhav, O. Rodriguez, N. Patel, A. Martin-Trujillo, M. Jain, H. Olsen, B. Paten, B. Ritz.


Thursday, October 17

9:00 AM–10:30 AM

Concurrent Platform Session C

40. Methods and Resources in Large-scale Population Data

Hall B, Level 1, Convention Center

Moderators: Kaixiong Ye, Univ Georgia, Athens
  Haichen Zhang, Univ Maryland, Baltimore

 

96/9:00 Open access to dbGaP new aggregated allele frequency for variant interpretation. L. Phan, H. Zhang, W. Qiang, E. Shekhtman, E. Moyer, E. Ivanchenko, D. Revoe, D. Shao, R. Villamarin, Y. Jin, M. Kimura, M. Feolo, J. Wang, N. Sharopova, M. Bihan, A. Sturcke, M. Lee, N. Popova, L. Hao, W. Wu, C. Bastiani, M. Ward, V. Lyoshin, K. Kaur, J.B. Holmes, B.L. Kattman.

97/9:15 Patterns of mitochondrial DNA variation across 15,000 individuals in the gnomAD database. N.J. Lake, K. Laricchia, G. Tiao, S. Pajusalu, L. Gauthier, M. Shand, J. Soto, J. Emery, D.G. MacArthur, V.K. Mootha, S.E. Calvo, M. Lek, gnomAD Consortium.

98/9:30 Public platform with 42,291 exome control samples enables association studies without genotype sharing. M. Artomov, A.A. Loboda, M.N. Artyomov, M.J. Daly.

99/9:45 Fast identity by descent detection across 500,000 UK Biobank samples reveals recent evolutionary history and population structure. J. Nait Saada, A. Gusev, P.F. Palamara.

100/10:00 Genome-wide rare variant analysis for thousands of phenotypes in 70,000+ exomes. E.T. Cirulli, S. White, R.W. Read, G. Elhanan, W.J. Metcalf, K.A. Schlauch, J.J. Grzymski, J. Lu, N.L. Washington.

101/10:15 Whole genome sequence association analysis of body mass index in 45,159 TOPMed participants. Z. Li, X. Li, H. Zhou, J. Brody, M. Graff, L. Lange, K. North, X. Lin, TOPMed Anthropometry-Adiposity Working Group.


Thursday, October 17

9:00 AM–10:30 AM

Concurrent Platform Session C

41. Somatic Mosaicism in Affected and Unaffected Individuals

Grand Ballroom A, Level 3, Convention Center

Moderators: Tasha Strande, Geisinger Hlth Syst, Danville
  Arupa Ganguly, Univ Pennsylvania Perelman Sch Med, Philadelphia

 

102/9:00 Somatic variation observed across tissues in healthy individuals. S. Vattathil, T.J. Comi, L. Chen, D.T. Akey, J.M. Akey.

103/9:15 Parental somatic mosaicism for CNV deletions: A need for more sensitive and precise detection methods in clinical diagnostics settings. Q. Liu, T. Wilson, J.A. Rosenfeld, C.M. Grochowski, C.A. Bacino, S.R. Lalani, A. Patel, A. Breman, J.L. Smith, S.W. Cheung, J.R. Lupski, W. Bi, P. Stankiewicz.

104/9:30 Genomic profiling of surgically excised brain tissue uncovers somatic mosaicism in seizure disorders. D.C. Koboldt, K.E. Miller, E. Crist, K.M. Leraas, T.A. Bedrosian, C.E. Cottrell, V. Magrini, D.R. Boué, C.R. Pierson, J. Leonard, R.K. Wilson, A. Ostendorf, E.R. Mardis.

105/9:45 Mosaic copy number variants are associated with autism spectrum disorder. M. Sherman, R. Rodin, G. Genovese, C. Dias, C. Walsh, P. Park, P.-R. Loh.

106/10:00 Single-cell analysis of human preimplantation embryos reveals widespread and complex patterns of chromosomal mosaicism. R.C. McCoy, M.R. Starostik.

107/10:15 Identification of low-level parental somatic mosaic SNVs and InDels in a large exome sequencing cohort of individuals with Mendelian disorders. T. Gambin, J.A. Karolak, Q. Liu, S.N. Jhangiani, Z.H. Coban Akdemir, J.R. Lupski, P. Stankiewicz.


Thursday, October 17

9:00 AM–10:30 AM

Concurrent Platform Session C

42. Genetics in Therapeutic Target Discovery

Grand Ballroom B, Level 3, Convention Center

Moderators: Hua Wang, Loma Linda Univ Children's Hosp
  Ellie Seaby, Broad Institute, Cambridge

 

108/9:00 Loss-of-function genomic variants with impact on liver-related blood traits highlight potential therapeutic targets for cardiovascular disease. J.B. Nielsen, O. Rom, I. Surakka, S.E. Graham, W. Zhou, L.G. Fritsche, S.A. Gagliano Taliun, C. Sidore, Y. Liu, M.E. Gabrielsen, A.H. Skogholt, B. Wolford, W. Overton, TOPMed. program, S. Lee, H.M. Kang, F. Cucca, O.L. Holmen, B.O. Åsvold, M. Boehnke, S. Kathiresan, G.R. Abecasis, Y.E. Chen, C.J. Willer, K. Hveem.

109/9:15 Computational discovery of candidates for drug repositioning for preterm birth. B. Le, S. Iwatani, R.J. Wong, D.K. Stevenson, M. Sirota.

110/9:30 Novel drug targets for ischemic stroke identified through Mendelian randomization analysis of the blood proteome. M. Chong, J. Sjaarda, M. Pigeyre, P. Mohammadi-Shemirani, R. Lali, A. Shoamanesh, H.C. Gerstein, G. Pare.

111/9:45 Proteome instability is an immunogenic therapeutic vulnerability in mismatch repair deficient cancer. N. Sahni, D. McGrail, J. Garnett, S. Kopetz, R. Broaddus, G. Mills, S.Y. Lin.

112/10:00 Genome wide association analysis in a Drosophila model of NGLY1 deficiency identifies NKCC1 as a modifier of disease and a novel NGLY1 substrate in Drosophila and mouse. E. Coelho, D. Talsness, K. Owings, K. Peralta, G. Mercenne, J. Pleinis, A. Zuberi, C. Lutz, A. Rodan, C.Y. Chow.

113/10:15 Identification of post-translational regulators of MeCP2 levels as potential therapeutic targets for MECP2 duplication syndrome. M. Zaghlula, J.-Y. Kim, L. Nitschke, H.H. Jeong, C.E. Alcott, J.-P. Revelli, Z. Liu, S.J. Elledge, H.Y. Zoghbi.


Thursday, October 17

9:00 AM–10:30 AM

Concurrent Platform Session C

43. Genetic Risk Factors for Cardiovascular Diseases

Grand Ballroom C, Level 3, Convention Center

Moderators: Clint Miller, Univ Virginia, Charlottesville
  Yasmmyn Salinas, Yale Univ, New Haven

 

114/9:00 Association of exome sequence variation with blood lipids in 170,000 individuals across multiple ancestries. G. Hindy, J. Flannick, P. Natarajan, M. Chaffin, A.V. Khera, G.M. Peloso, on behalf of the AMP-T2D-GENES and TOPMed Lipids Working Groups.

115/9:15 Trans-ethnic meta-analysis of cholesterol and triglyceride levels from 1.6 million individuals. S.E. Graham, G.J.M. Zajac, I. Surakka, X. Li, E. Marouli, I. Ntalla, S. Ramdas, X. Yin, X. Zhu, T.L. Assimes, C.D. Brown, P. Deloukas, A.P. Morris, Y.V. Sun, G. Abecasis, G. Peloso, S. Kathiresan, C.J. Willer, Million Veteran Program, Global Lipids Genetics Consortium.

116/9:30 Integrated statistical and molecular analysis of a missense variant in the PROCR gene that increases risk for venous thromboembolism but protects against coronary artery disease. D. Stacey, L. Chen, J.M.M. Howson, A.M. Mason, S. Burgess, S. MacDonald, J. Langdown, H.L. McKinney, K. Downes, N. Farahi, C. Summers, J. Danesh, D.S. Paul, INVENT, ARIC study, INTERVAL study.

117/9:45 Kidney genes as drivers of heritable predisposition to hypertension: Multi-omic analysis of loci from genome-wide association studies. J.M. Eales, X. Jiang, X. Xu, S. Saluja, E. Cano-Gamez, H. Guo, G. Trynka, A.P. Morris, N.J. Samani, F.J. Charchar, M. Tomaszewski, TRANSLATE consortium.

118/10:00 Mendelian randomization supports causal associations between lipids and adiposity in non-alcoholic fatty liver disease. K.A.B. Gawronski, M. Vujkovic, M. Serper, D. Kaplan, R. Carr, K. Lee, Q. Shao, D. Miller, P. Reaven, L.S. Phillips, C. O'Donnell, J.B. Meigs, P. Wilson, T. Assimes, Y.V. Sun, J. Huang, K. Cho, J. Lee, P. Tsao, D. Rader, C. Brown, S. Damrauer, D. Saleheen, J. Lynch, K. Chang, B.F. Voight.

119/10:15 Mendelian randomization analyses reveal a causal effect of thyroid function on cardiovascular risk factors and diseases. E. Marouli, A. Kus, F. Del Greco, L. Chaker, R. Peeters, A. Teumer, M. Medici, P. Deloukas.


Thursday, October 17

9:00 AM–10:30 AM

Concurrent Platform Session C

44. Genetic Regulatory Variants and Complex Trait Associations

Room 310A, Level 3, Convention Center

Moderators: Luke Jostins-Dean, Univ Oxford, UK
  Yanyu Liang, Univ Chicago

 

120/9:00 Multi-tissue analysis reveals short tandem repeats as ubiquitous regulators of gene expression and complex traits. M. Gymrek, S. Feupe Fotsing, C. Wang, S. Saini, R. Yanicky, S. Shleizer-Burko, A. Goren.

121/9:15 Cellular deconvolution of GTEx tissues powers eQTL studies to discover thousands of novel disease and cell-type associated regulatory variants. M. Donovan, A. D’Antonio-Chronowska, M. D’Antonio, K. Frazer.

122/9:30 Does sex-specificity of eQTLs propagate to complex traits? E. Porcu, A. Claringbould, K. Lepik, R. Jansen, L. Franke, F.A. Santoni, A. Reymond, Z. Kutalik, BIOS Consortium.

123/9:45 Causal mediation analysis identifies a comprehensive map of gene-level polygenicity and pleiotropy across 43 traits in 49 tissues. Y. Park, A.K. Sarkar, L. He, K.T. Nguyen, N. Daskalakis, M. Kellis, GTEx Consortium.

124/10:00 Identifying the genes and cell types affected by genetic risk loci for primary sclerosing cholangitis. E.C. Goode, L. Moutsianas, L. Fachal, T. Raine, S.M. Rushbrook, C.A. Anderson.

125/10:15 ADAR-mediated editing of a microRNA in bronchial epithelial cells is associated with severe asthma in children of asthmatic mothers. K.M. Magnaye, D.K. Hogarth, E.T. Naureckas, S.R. White, C. Ober.


Thursday, October 17

9:00 AM–10:30 AM

Concurrent Platform Session C

45. Strategies to Improve Genetic Counseling Practice and Education

Room 360D, Level 3, Convention Center

Moderators: Charles Wray, Jackson Lab, Bar Harbor
  Andrew Faucett, Geisinger Hlth Sys, Danville

 

126/9:00 Development and psychometric analysis of instrument to measure high school genetics knowledge. GLASS: Genetics Literacy Assessment for Secondary Schools. K. Ormond, J. Keyes, R.J. Okamura, S. Lee, M. Dougherty, B. Domingue.

127/9:15 Preparing medical laboratory scientists for the genomic era: A 5-year comprehensive education strategy towards professional competencies in variant interpretation. N.P. Thorne, A. Nisselle, S. Lunke, A. Fellowes, M. Martyn, A. Roesley, C. McEwen, M. Fanjul Fernandez, T.Y. Tan, D. Liddicoat, Z. Stark, E. Thompson, F. Maher, F. Cunningham, I. Macciocca, G. Reid, P. James, J. Hodgson, C. Gaff, Diagnostic Advisory Group.

128/9:30 Are hospitals prepared to implement rapid whole-genome sequencing (WGS) in NICU/PICU settings? Healthcare provider perspectives from the frontline. M. Brown, A.M. Li-Rosi, S. Hussain, R. Veith, A. Jorgenson, D. Salyakina, J. McCafferty, K. Schain, A. Quittner, Nicklaus Children's Personalized Medicine Clinical Team.

129/9:45 The development of the clinician-reported genetic testing utility index (C-GUIDE): A novel strategy for measuring the clinical utility of genetic testing. R.Z. Hayeems, S. Luca, W.J. Ungar, A. Bhatt, L. Chad, E. Pullenayegum, M.S. Meyn.

130/10:00 Group counseling by webinar: An efficient approach to pre-test counseling. B. Swope, E.S. Gordon, C.A. Fine, L. Myers, S.M. Weissman, J. Bailey, A. Fan, E. Jordan, B. LeLuyer, A.F. Rope, H. Shabazz, S.B. Bleyl.

131/10:15 Missed diagnoses: Clinically relevant lessons learned through cases diagnosed by the Undiagnosed Diseases Network. H. Cope, R. Spillmann, J. Sullivan, J.A. Rosenfeld, E. Brokamp, R. Signer, S. Lincoln, J. Martinez-Agosto, K. Dipple, V. Shashi, Undiagnosed Diseases Network.


Thursday, October 17

9:00 AM–10:30 AM

Concurrent Platform Session C

46. Genetics of Prostate Cancer

Room 361D, Level 3, Convention Center

Moderators: Clara Cieza-Borrella, Univ London, UK
  Nicholas Larson, Mayo Clinic, Rochester

 

132/9:00 Genome-wide association meta-analysis of over 237,000 breast, prostate, ovarian, and endometrial cancer cases and 317,000 controls identifies 128 regions containing associations with multiple cancers. S. Kar, S. Lindström, J. Dennis, K. Michailidou, R. Hung, D.F. Easton, J. Simard, A. Spurdle, T. O'Mara, R. Eeles, B. Pasaniuc, P. Kraft, P. Pharoah, on behalf of the BCAC, OCAC, ECAC, GAME-ON, PRACTICAL, CAPS and PEGASUS consortia.

133/9:15 Transcriptome-wide association study in African Americans identifies associations with prostate cancer. P.N. Fiorica, M. Abdul Sami, J.D. Morris, H.E. Wheeler.

134/9:30 Genome-wide germline correlates of the epigenetic landscape of prostate cancer. K.E. Houlahan, Y. Shiah, A. Gusev, B. Pasaniuc, M.L. Freedman, H.H. He, R.G. Bristow, P.C. Boutros.

135/9:45 Integrating polygenic risk scores information with somatic and transcriptome data to unravel the polygenic architecture of prostate cancer. C. Hicks, T.K.K. Mamidi, J. Wu, E.J. Nicklow.

136/10:00 CRISPRi screen of risk-associated cis-regulatory elements reveals 3D genome dependent causal mechanisms in prostate cancer. M. Ahmed, F. Soares, J. Xia, P. Su, H. Guo, J.T. Hua, M. Wang, S. Chen, S. Zhou, J. Petricca, Y. Zeng, Y. Zhu, T. Severson, Y. Tian, A. Bosch, K.E. Houlahan, M. Lupien, W. Zwart, M.L. Freedman, T. Wang, P.C. Boutros, M.J. Walsh, L. Wang, G.H. Wei, H.H. He.

137/10:15 Interim results from the IMPACT study: Evidence for PSA screening in BRCA2 mutation carriers. E.K. Bancroft, E.C. Page, M.N. Brook, M. Assel, J. Offman, Z. Kote-Jarai, A. Vickers, H. Lilja, R.A. Eeles, The IMPACT Study Steering Committee and Collaborators.


Thursday, October 17

9:00 AM–10:30 AM

Concurrent Platform Session C

47. Genetic Mechanisms of Autism and Related Disorders

Room 370A, Level 3, Convention Center

Moderators: Virginia Kimonis, UC Irvine Med Center
  Volkan Okur, Baylor Col Med, Houston

 

138/9:00 Decreased nuclear PTEN increases microglia activation and synaptic pruning in a murine model with autism-like phenotype. N. Sarn, R. Jaini, S. Thacker, H. Lee, C. Eng.

139/9:15 Identification of human-specific mRNA targets of fragile X mental retardation protein. Y. Li, Z. Li, Y. Kang, E. Allen, H. Wu, Z. Wen, P. Jin.

140/9:30 Sex-specific brain transcriptome dysfunction burden in schizophrenia, autism spectrum disorder, and bipolar disorder. Y. Xia, C. Chen, Y. Chen, Y. Jiang, C. Liu, psychENOCODE.

141/9:45 Spatiotemporal gene expression pattern predicts of autism risk genes. S. Chen, Y. Shen.

142/10:00 Insights into the genetic architecture of autism from exome and genome sequencing of over 60,000 individuals. F.K. Satterstrom, J. Fu, H. Brand, J.A. Kosmicki, H. Wang, X. Zhao, R.L. Collins, M.S. Breen, S. De Rubeis, C.E. Carey, C. Stevens, C. Cusick, E.B. Robinson, A.D. Børglum, D.J. Cutler, J.D. Buxbaum, K. Roeder, B. Devlin, S.J. Sanders, M.J. Daly, M.E. Talkowski, Autism Sequencing Consortium.

143/10:15 No consistent evidence for effect of rare pathogenic and likely pathogenic exonic variation in bipolar disorder. A.E. Locke, X. Jia, F. Goes, W. Wang, D.S. Palmer, B.M. Neale, S.M. Purcell, N. Risch, C. Schaefer, E.A. Stahl, L.J. Scott, P. Zandi, Bipolar Sequencing Consortium Case/Control Working Group.


Thursday, October 17

9:00 AM–10:30 AM

Concurrent Platform Session C

48. Causal Genes in Skeletal Development

Room 371A, Level 3, Convention Center

Moderators: Yangjin Bae, Baylor Col Med, Houston
  Struan F. Grant, CHOP

 

144/9:00 Longitudinal genome-wide association study identifies novel loci and functional follow-up implicates putative effector genes for pediatric bone accrual. D.L. Cousminer, Y. Wagley, J.A. Pippin, G.P. Way, S.E. McCormack, J.A. Mitchell, J.M. Kindler, H.J. Kalkwarf, J.M. Lappe, M.E. Johnson, H. Hakonarson, V. Gilsanz, J.A. Shepherd, S.E. Oberfield, C.S. Greene, B.F. Voight, A.D. Wells, B.S. Zemel, K.D. Hankenson, S.F.A. Grant.

145/9:15 Network analysis identifies key genetic drivers of bone mass. B.M. Al-Barghouthi, G. Calabrese, L. Mesner, C.J. Rosen, M.C. Horowitz, M.L. Bouxsein, D. Brooks, S.M. Tommasini, C.R. Farber.

146/9:30 Large-scale global multi-ethnic GWAS doubles the number of osteoarthritis loci and identifies new treatment targets. C. Boer, K. Hatzikotoulas, L. Southam, L. Stefánsdóttir, U. Styrkársdóttir, J.B.J. van Meurs, E. Zeggini, Genetics of Osteoarthritis Consortium.

147/9:45 From GWAS to causal variants: Separate regulatory base pairs at GDF5-UQCC1 underlie common knee osteoarthritis risk and developmental dysplasia of the hip. T.D. Capellini, P. Muthuirulan, Z. Liu, A.M. Kiapour, J. Cao, J. Sieker, S. Yarlagadda, D.E. Maridas, V. Rosen, M. Young.

148/10:00 Role of MMP2 in early craniofacial development in zebrafish. B. Tandon, Q. Yuan, L. Maili, S.H. Blanton, G.T. Eisenhoffer, A. Letra, J.T. Hecht.

149/10:15 Feline precision medicine implicates UGDH as a novel gene for disproportionate dwarfism. L. Lyons, R. Buckley, R. Grahn, 99 Lives Consortium.


Thursday, October 17

11:00 AM–12:30 PM

Concurrent Platform Session D

49. Variants Associated with Cancer in Large Cohorts

Hall B, Level 1, Convention Center

Moderators: Harry Ostrer, Albert Einstein Col Med, New York
  Burcu Darst, Univ Southern California, Los Angeles

 

150/11:00 Comprehensive genetic analysis yields new insights into the etiologies of right-sided and left-sided colorectal cancer. J.R. Huyghe, T.A. Harrison, S.A. Bien, H. Hampel, J.C. Figueiredo, S.L. Schmit, C. Qu, Y. Lin, J.A. Baron, A.J. Cross, B. Diergaarde, D. Duggan, S. Harlid, D.M. Levine, L.C. Sakoda, M.L. Slattery, F.J.B. van Duijnhoven, B. Van Guelpen, A.T. Chan, M. Hoffmeister, M.A. Jenkins, R.E. Schoen, P. Vodicka, E. White, G. Casey, R.B. Hayes, P.A. Newcomb, S.B. Gruber, L. Hsu, U. Peters, on behalf of CCFR, CORECT and GECCO.

151/11:15 GWAS for non-melanoma skin cancer in the UK Biobank cohort: Novel loci include the checkpoint inhibitor CTLA4, where common variants protect against skin cancer and increase risk for auto-immune traits. V. Agarwala, Y. Tanigawa, G. Venkataraman, M. Aguirre, M. Rivas.

152/11:30 Discovering susceptibility genes shared by neural crest derived tumors neuroblastoma and melanoma. M. Avitabile, M. Succoio, A. Testori, A. Cardinale, Z. Vaksman, V.A. Lasorsa, S. Cantalupo, M. Esposito, F. Cimmino, A. Montella, D. Formicola, J. Koster, V. Andreotti, P. Ghiorzo, M.F. Romano, S. Staibano, M. Scalvenzi, F. Ayala, H. Hakonarson, V.M. Corrias, M. Devoto, M.H. Law, M.M. Iles, K. Brown, S. Diskin, N. Zambrano, A. Iolascon, M. Capasso.

153/11:45 Discovery of novel rare and common genetic variants for colorectal cancer using TOPMed whole genome sequencing data. X. Wang, T.A. Harrison, J. Huyghe, C. Qu, S. Chen, S. Bien, D.V. Conti, C. Kooperberg, M.J. Gunter, V. Moreno, P.D.P Pharoah, K.R. Curtis, T.O. Keku, S.L. Schmit, P.C. Scacheri, A. Kundaje, S.J. Gallinger, M.A. Jenkins, G.R. Abecasis, D.A. Nickerson, H.M. Kang, G. Casey, S.B. Gruber, L. Hsu, U. Peters.

154/12:00 Polygenic risk scores improve prediction and risk stratification: Results from a pan-cancer analysis in the UK Biobank. L. Kachuri, R.E. Graff, K. Smith-Byrne, S.R. Rashkin, E. Ziv, J.S. Witte, M. Johansson.

155/12:15 Hundreds of GWAS on a deeply-imputed cohort of 117,242 Ashkenazi Jews identify novel associations with uncommon and rare coding variants across a wide range of diseases. A. Kleinman, V. Vacic, S. Pitts, R. Gentleman, 23andMe Research Team.


Thursday, October 17

11:00 AM–12:30 PM

Concurrent Platform Session D

50. Dominant and Recessive: Not that Simple? Lessons from Clinics and Cohorts

Grand Ballroom A, Level 3, Convention Center

Moderators: Joseph Shieh, UCSF
  Isabelle Thiffault, Children's Mercy Hosp, Kansas City

 

156/11:00 Characteristics of genes that underlie both recessive and dominant Mendelian conditions. J.X. Chong, M.J. Bamshad, University of Washington Center for Mendelian Genomics.

157/11:15 Cohort analysis/reanalysis identifies CDH11 a novel gene for Teebi hypertelorism syndrome. D. Li, E.J. Bhoj, C. Seiler, M.E. March, M.R. Battig, P. Sleiman, E. Bedoukian, L.C. Pyle, M. Wilson, C. Patel, J. Christodoulou, E.H. Zackai, H. Hakonarson.

158/11:30 Known disease variants in a population-wide analysis of 135,638 Finns. H.O.H Heyne, S.M.L Lemmelae, J.K. Karjalainen, A.S.H. Havulinna, A.P. Palotie, M.J.D. Daly.

159/11:45 Analysis of phenotype penetrance in heterozygous carriers of autosomal recessive disorders using whole genome sequencing in a precision medicine clinic. Y.-C.C. Hou, H.-C. Yu, R. Martin, E.T. Cirulli, N.M. Schenker-Ahmed, M. Hicks, I.V. Cohen, T.J. Jönsson, R. Heister, L. Napier, C.L. Swisher, S. Dominguez, H. Tang, W. Li, B.A. Perkins, J. Barea, C. Rybak, E. Smith, K. Duchicela, M. Doney, P. Brar, N. Hernandez, E.F. Kirkness, A.M. Kahn, J.C. Venter, D.S. Karow, C.T. Caskey.

160/12:00 Defining the phenotypic signature of CFTR mutation carriers in the UK Biobank. Y. Lin, N. Panjwani, F. Mohsin, M. Sutton, J. Dennis, J.M. Rommens, L. Sun, L.J. Strug.

161/12:15 Identification of asymptomatic individuals with homozygous deletions of SMN1 via routine carrier screening. J. Chaperon, E. Hendricks, M. Westmeyer, S. Leonard.


Thursday, October 17

11:00 AM–12:30 PM

Concurrent Platform Session D

51. Chromatin Accessibility and Spatial Genome Organization in Disease

Grand Ballroom B, Level 3, Convention Center

Moderators: Carolyn Brown, Univ British Columbia, Vancouver, Canada
  Casey Thornton, Oregon Hlth Sci Univ, Portland

 

162/11:00 Cell type specificity of intralocus interactions reveals novel disease mechanisms. O. Corradin, D.C. Factor, M. Madhavan, S. Nisraiyya, A. Barbeau, P. Hall, F.J. Najm, T.E. Miller, Z.S. Nevin, R.T. Karl, K.C. Allan, M.S. Ellit, B. Lima, K. Hazel, A. Hoang, G.K. Dhillon, C. Volsko, C.F. Bartels, E. Shick, D.J. Adams, R. Dutta, A. Kozlenkov, S. Dracheva, P.C. Scacheri, P.J. Tesar.

163/11:15 Mechanistic dissection of chromatin topology disruption as an indirect, strong effect driver of neurodevelopmental disorders. K. Mohajeri, E. D'haene, R. Yadav, H. Gu, B. Menten, A. Presser Aiden, C. Lowther, S. Erdin, M. Moyses Oliveria, P. Boone, E. Lieberman-Aiden, J. Gusella, S. Vergult, M. Talkowski.

164/11:30 Targeted delivery of chimeric pioneer factors reveals differential activity and chromatin accessibility dependent upon genetic context. Y. Tan, J.H. Goell, I.B. Hilton.

165/11:45 Incorporation of spatial mapping and confirmation of gene signatures by a multiplex in situ hybridization technology into single cell RNA sequencing workflows. J. Phatak, H. Lu, L. Wang, H. Zong, M. Rouault, C. May, X. Ma, C. Anderson.

166/12:00 Chromatin activity at GWAS loci identifies T cell states driving complex immune diseases. B. Soskic, E. Cano-Gamez, D.J. Smyth, W.C. Rowan, N. Nakic, J. Esparza-Gordillo, L. Bossini-Castillo, D.F. Tough, C. Larminie, P.G. Bronson, D. Wille, G. Trynka.

167/12:15 Single cell chromatin accessibility in human pancreatic islets reveals cell type- and state-specific regulatory programs of diabetes risk. D. Gorkin, J. Chiou, C. Zeng, Z. Cheng, J. Han, M. Schlichting, S. Huang, J. Wang, Y. Sui, A. Deogaygay, M. Okino, Y. Qiu, Y. Sun, P. Kudtarkar, R. Fang, S. Preissl, M. Sander, K.J. Gaulton.


Thursday, October 17

11:00 AM–12:30 PM

Concurrent Platform Session D

52. Considerations With Using Polygenic Risk Scores

Grand Ballroom C, Level 3, Convention Center

Moderators: Themistocles Assimes, Stanford Univ
  Alicia Martin, Massachusetts Gen Hosp, Boston

 

168/11:00 Applying confidence intervals to clinical polygenic risk scores in 60,000 exome+ sequenced individuals. K. Dunaway, A. Bolze, J. Rizko, S. Luo, S. White, L. Sharma, N. Washington, W. Lee, J. Lu.

169/11:15 Sibling difference analyses reveal polygenic risk score confounding. P.K. Joshi, P.R.H.J Timmers, D.W. Clark, J.F. Wilson.

170/11:30 Pervasive hidden founder effects in large population scale biobanks impact polygenic load and risk estimation. G.M. Belbin, A. Moscati, I. Overcast, M. Daya, G. Wojcik, N. Zaitlen, I. Mathieson, C.R. Gignoux, E.E. Kenny.

171/11:45 Machine-learning based deconvolution of biobank-driven GWAS data with 170,000 individuals enlightens the finest-scale genetic, evolutional, and polygenic risk score divergence within Japanese population. J. Hirata, S. Sakaue, K. Suzuki, M. Akiyama, M. Kanai, M. Hirata, K. Matsuda, Y. Murakami, Y. Kamatani, Y. Okada.

172/12:00 Optimisation of polygenic risk scores across 16 common diseases using cross-trait and cross-ethnic information. V. Plagnol, E. Kraphol, P. Sorensen, C.C. Spencer, A. Heger, M. Sivley, R. Moore, G. Lunter, M. Weale, P. Donnelly.

173/12:15 Screening human embryos for polygenic traits has limited utility. S. Carmi, E. Karavani, O. Zuk, D. Zeevi, G. Atzmon, N. Barzilai, N.C. Stefanis, A. Hatzimanolis, N. Smyrnis, D. Avramopoulos, L. Kruglyak, M. Lam, T. Lencz.


Thursday, October 17

11:00 AM–12:30 PM

Concurrent Platform Session D

53. Genetics of Cardiac and Vascular Disorders

Room 310A, Level 3, Convention Center

Moderators: Cassie Spracklen, Univ Massachusetts Amherst
  Casey Romanoski, Univ Arizona, Tucson

 

174/11:00 Rapid whole genome sequencing (rWGS) impacts resource utilization and improves management of critically ill infants with congenital heart disease. N. Sweeney, N. Nahas, S. Chowdhury, S. Caylor, J. Caciki, S. Batalov, Y. Ding, N. Veeraraghavan, D. Dimmock, S. Kingsmore, Rady Children’s Institute for Genomic Medicine.

175/11:15 Polygenic architecture of computationally derived aortic diameter from 20,939 British adults predicts the risk for aortic aneurysm and dissection. C. Tcheandjieu, K. Xiao, H. Tejeda, E. Ingelsson, J. Fries, J. Priest.

176/11:30 Large-scale GWAS and multi-omic follow-up reveal new mechanisms for heart failure. M. Arvanitis, Y. Zhang, B. Ren, W.S. Post, A. Battle.

177/11:45 Overlap of fetal-specific cardiac regulatory variants and GWAS lead variants supports fetal origins of cardiovascular disease. K.A. Frazer, M.K.R. Donovan, W.W. Young Greenwald, D. Jakubosky, P. Benaglio, E.N. Smith, A. D’Antonio-Chronowska, D. D’Antonio.

178/12:00 Comprehensive epigenomic and transcriptomic profiling of human embryonic heart reveals the regulatory landscape of heart development and implicates noncoding sequences in congenital heart defects. J. VanOudenhove, A. Wilderman, T. Yankee, J. Cotney.

179/12:15 Dynamic genetic regulation of gene expression during cellular differentiation. K. Rhodes, R. Elorbany, B. Strober, N. Krishnan, K. Tayeb, A. Battle, Y. Gilad.


Thursday, October 17

11:00 AM–12:30 PM

Concurrent Platform Session D

54. Evolutionary Mechanisms Underlying Phenotypic Change

Room 360D, Level 3, Convention Center

Moderators: Michele Daya, Univ Colorado, Aurora
  Zachary A. Szpiech, Auburn Univ

 

180/11:00 Population-specific causal disease effect sizes at loci impacted by negative selection. H. Shi, S. Gazal, M. Kanai, A.P. Schoech, Y. Okada, S.S. Kim, A.L. Price.

181/11:15 Strong selection for cold and carbohydrate diets in ancient Eurasian. Y. Souilmi, R. Tobler, A. Johar, M. Williams, S. Grey, J. Teixeira, A. Rohrlach, G. Gower, C. Turney, M. Cox, W. Haak, C.D. Huber, A. Cooper.

182/11:30 The effects of mutation subtype on the allele frequency spectrum and population genetics inference. K. Liao, J. Carlson, S. Zöllner, The BRIDGES Consortium.

183/11:45 Identifying and characterising germline hypermutators. J. Kaplanis, E. Prigmore, P. Short, J. Korbel, M. Hurles.

184/12:00 The evolutionary impact of an ancient deletion polymorphism in the human growth hormone receptor gene. O. Gokcumen, S. Resendez, M. Saitou, K. Dean, F. Wu, X. Mu.

185/12:15 Reconstructing Denisovan anatomy using DNA methylation maps. D. Gokhman, N. Mishol, M. de Manuel, D. de Juan, J. Shuqrun, T. Marques-Bonet, Y. Rak, L. Carmel.


Thursday, October 17

11:00 AM–12:30 PM

Concurrent Platform Session D

55. Genetic Effects on Transcriptome and Genome Traits

Room 361D, Level 3, Convention Center

Moderators: Ayellet Segre, Harvard Med Sch, Boston
  Malene Lindholm, Stanford Univ

 

186/11:00 Combining ATAC-seq and high-throughput reporter assays to identify sequences, factors, and genetic variants that regulate gene expression in different environmental contexts. F. Luca, C. Kalita, A. Alazizi, A. Findley, X. Wen, R. Pique-Regi.

187/11:15 Exon-skipping regulation in complex disease. R. Liu, A. Byrnes, M. Daly, H. Huang.

188/11:30 Genetic basis of alternative polyadenylation is an emerging molecular phenotype for human traits and diseases. L. Li, Y.P. Gao, F.L. Peng, EricJ. Wagner, W. Li.

189/11:45 N6-methyladenosine (m6A) methylation of mRNAs makes a large contribution to genetics of common diseases. K. Luo, Z. Zhang, M. Qiu, H. Shi, Y. Zou, G. Wang, A. Zhu, M. Qiao, Z. Li, M. Stephens, X. He, C. He.

190/12:00 The contribution of miRNA regulation to inter-individual and inter-population variability in immune responses. M. Rotival, M. Silvert, K.J. Siddle, J. Pothlichet, H. Quach, L. Quintana-Murci.

191/12:15 The genetic architecture of DNA replication timing in human pluripotent stem cells. Q. Ding, A. Bracci, M. Edwards, M. Hulke, Y. Hu, Y. Tong, X. Zhu, J. Hsiao, C. Charvet, S. Ghosh, R. Handsaker, M. Stephens, S. McCarroll, K. Eggan, Y. Gilad, F. Merkle, J. Gerhardt, D. Egli, A. Clark, A. Koren.


Thursday, October 17

11:00 AM–12:30 PM

Concurrent Platform Session D

56. Functional Assays for Clinically Relevant Variant Interpretation

Room 370A, Level 3, Convention Center

Moderators: Claudia Carvalho Fonseca, Baylor Col Med, Houston
  Karen Gripp, Duport Hosp, Wilmington

 

192/11:00 A multi-model approach for deep functional variomic profiling of ASD-associated PTEN missense mutations identifies multiple molecular mechanisms underlying protein dysfunction. F. Meili, K. Post, M. Belmadani, P. Ganguly, R. Dingwall, T. McDiarmid, C. Harrington, M. Edwards, B. Young, A. Niciforovic, B. Callahan, S. Rogic, W. Meyers, A. Cau, T. O'Connor, C. Rankin, S.X. Bamji, D.W. Allen, C. Loewen, P. Pavlidis, K. Haas.

193/11:15 Integrating molecular and clinical phenotypes towards clinical insight on genotype-phenotype relationships for missense germline PTEN variation. S. Thacker, T. Mighell, I.N. Smith, M. Seyfi, B.J. O'Roak, C. Eng.

194/11:30 A humanized yeast assay to define dominant-negative properties of pathogenic alleles in highly conserved, essential genes. R. Meyer-Schuman, A. Antonellis.

195/11:45 Modeling VUSes in a clinically relevant time frame. M. Bainbridge, J. Friedman, C. Hopkins, K. McCormick, T. Brock, D. Dimmock, S. Kingsmore, C. Hobbs.

196/12:00 Phenotype-driven blood biomarker and muscle functional genomics significantly increase neuromuscular disease diagnosis of >400 patients by resolving VUSs and multi-gene inheritance. S. Chakravorty, K. Berger, S.P.V. Shenoy, B.R.R. Nallamilli, L. Rufibach, S. Shira, M. Wicklund, M. Harms, T. Mozaffar, D. Arafat, G. Gibson, M. Hegde, Jain COS Consortium.

2418/12:15 A high-throughput assay to test functional significance of BRCA1 RING domain missense substitutions: Methodology, calibration, and results. K.A. Clark, A.M. Paquette, K. Tao, J.S. Rosenthal, A.K. Snow, J. Unger, K.M. Boucher, J. Gertz, A. Thomas, K.E. Varley, S.V. Tavtigian.


Thursday, October 17

11:00 AM–12:30 PM

Concurrent Platform Session D

57. Solving the Unsolved: Strategies for Increasing Diagnostic Yield

Room 371A, Level 3, Convention Center

Moderators: Bing Huang, LabCorp, Burlington
  Stuart Scott, Mount Sinai Sch Med, New York

 

198/11:00 Utilizing RNA sequencing for the diagnosis of unsolved cases of Cornelia de Lange syndrome and related neurodevelopmental disorders. S. Rentas, K. Rathi, M. Kaur, P. Raman, I.D. Krantz, M. Sarmady, A. Abou Tayoun.

199/11:15 Retrospective whole exome sequencing analysis reveals variants in BAF complex genes associated with global developmental delay, epilepsy, and dysmorphism. J. Lattier, L. Meng, F. Xia, P. Liu, W. Bi, B. Yuan, V. Patel, D. Scott, R. Marom, M. Wangler, J. Mokry, C. Eng, R. Xiao.

200/11:30 Skewed X-chromosome inactivation in patients with non-diagnostic exome sequencing: Additional diagnostic yield. I.M. Campbell, L. Dong, T. Pinnheiro, J. Yutz, A. Ganguli, E.J. Bhoj.

201/11:45 Identifying diagnoses beyond the exome: Lessons from challenging cases with compelling clinical phenotypes. A. O'Donnell-Luria, M.H. Wojcik, K.R. Chao, J.K. Goodrich, L.S. Pais, E. England, E.G. Seaby, A.B. Byrne, B.B. Cummings, R.L. Collins, M. Lek, L. Gallacher, T.Y. Tan, K.M. Bujakowska, E.A. Pierce, P.B. Agrawal, C.A. Walsh, J.M. Verboon, V.G. Sankaran, C. Barnett, H. Scott, W.K. Chung, E.A. Estrella, C.C. Bruels, P.B. Kang, S. Pajusalu, K. Ounap, A.K. Lovgren, H.L. Rehm, D.G. MacArthur.

202/12:00 Broad-scale untargeted metabolomic profiling improves diagnosis of inborn errors of metabolism. N. Liu, J. Xiao, C. Gijanavekar, K.E. Glinton, B.J. Shayota, Y. Yang, K.L. Pappan, A.D. Kennedy, M.F. Wangler, L.C. Burrage, F. Scaglia, W.J. Craigen, C. Soler, L.T. Emrick, F. Xia, V.R. Sutton, Q. Sun, S.H. Elsea.

203/12:15 Cascading after peri-diagnostic cancer genetic testing: An alternative to population based screening. K. Offit, S. Mukherjee, K. Tkachuk.


Thursday, October 17

4:15 PM–5:15 PM

Concurrent Platform Session E

58. CRISPR-Based Approaches to Study Genome Function

Hall B, Level 1, Convention Center

Moderators: Kay-Marie Lamar, Northwestern Univ, Chicago
  Nara Sobreira, Johns Hopkins Univ, Baltimore

 

204/4:15 Evaluation of the cutting efficiencies of sgRNAs in CRISPR/Cas editing experiments utilizing droplet digital PCR (ddPCR). E. Cerveira, M. Ryan, L. Bellfy, A. Mil-Homens, Q. Zhu, C. Lee, C. Zhang.

205/4:30 CRISPR-capture: A novel, low-cost, and scalable method for targeted sequencing. T.L. Mighell, C.A. Thornton, B.L. O'Connell, R.M. Mulqueen, C.V. Miller, A.C. Adey, D. Doherty, B.J. O'Roak.

206/4:45 Interrogating regulatory consequences of genetic variation in DNA associated proteins. C. Wu, S. Shleizer-Burko, A. Goren, M. Gymrek.

207/5:00 Deciphering the histone acetyl code in human cells with dCas9-based epigenome editing. K. Wang, J. Li, I.B. Hilton.


Thursday, October 17

4:15 PM–5:15 PM

Concurrent Platform Session E

59. Mechanisms of Rare Neurogenetic Disorders

Grand Ballroom A, Level 3, Convention Center

Moderators: Lisa Emrick, Baylor Col Med, Houston
  Martin Breuss, UCSD

 

208/4:15 Incompletely penetrant rare coding variants account for a major fraction of patients with undiagnosed developmental disorders. K.E. Samocha, P. Danecek, E.J. Gardner, H.C. Martin, P.J. Short, M.E. Hurles, on behalf of the Deciphering Developmental Disorders study.

209/4:30 Dysfunction in neurons and glia reveals that distinct PIGA deficiency phenotypes arise from independent cell types. C.Y. Chow, M. Haller, E. Coehlo, J. Plenis, O. Kanca, H. Bellen, A. Rodan.

210/4:45 The ZBTB7B-RSK3 pathway regulates ATXN1, the protein driving neurodegeneration in an inherited ataxia. W. Lee, L. Lavery, M. Rousseaux, I. Al-Ramahi, Y. Wan, W. Kim, C. Adamski, V. Bondar, H. Orr, Z. Liu, J. Botas, H. Zoghbi.

211/5:00 Rare CDC20B variants in juvenile myoclonic epilepsy. P. Barak, P. Satishchandra, S. Sinha, G. Kuruttukulam, M. Kaur, A. Anand.


Thursday, October 17

4:15 PM–5:15 PM

Concurrent Platform Session E

60. A Deep Dive into Deep Learning

Grand Ballroom B, Level 3, Convention Center

Moderators: Joanne Berghout, Univ Arizona, Tucson
  Sarah Gagliano Taliun, Univ Michigan, Ann Arbor

 

212/4:15 Deep tensor factorization characterizes the human epigenome through imputation of thousands of genome-wide epigenomics and transcriptomics experiments. J. Schreiber, J. Bilmes, W. Noble.

213/4:30 Using a deep neural network (DNN) based classifier to predict primary sites of cancers of unknown primary. I. Moon, A. Gusev.

214/4:45 Using deep learning and genetic big data to predict complex disease risk. D. Li, T. Haritunians, M. Daly, D. McGovern, IIBDGC Consortium.

215/5:00 A deep learning method for inferring the strength and location of sweeps using local genealogies based on the ancestral recombination graph. H.A. Hejase, A. Siepel.


Thursday, October 17

4:15 PM–5:15 PM

Concurrent Platform Session E

61. Dissecting Molecular Pathways in Schizophrenia

Grand Ballroom C, Level 3, Convention Center

Moderators: Paula Ramos, Med Univ South Carolina, Charleston
  Dalila Pinto, Icahn Sch Med Mount Sinai, New York

 

216/4:15 Population differences in brain regulatory profiles influence risk of schizophrenia. S. Liu, Y. Chen, F. Wang, Y. Jiang, F. Duan, R. Kopp, C. Liu, C. Chen, PsychENCODE Consortium.

217/4:30 Sex-differences in brain development correspond to sex-differences in the age of onset for schizophrenia. C. Jiao, R. Kopp, L. Vivid, C. Chen, C.Y. Liu.

218/4:45 Refining cell populations and fine-mapping variants for schizophrenia and bipolar disorder using mouse open chromatin profiles. P.W. Hook, A.S. McCallion.

219/5:00 From genetic risk variants to convergent protein networks: An integrative approach to elucidate the causal molecular mechanisms of schizophrenia. A. Kim, E. Nacu, E. Malolepsza, N. Petrossian, W. Crotty, T. Suh, J. Riseman, T. Singh, R. Liu, S. Muller, G. Pintacuda, M. Johnson, K. Sharma, R. Huganir, B. Stevens, M. Daly, H. Huang, M. Schenone, S. Egri, B. Tanenbaum, A. Appfel, C. Stanclift, J. Jaffe, K. Lilliehook, K. Eggan, K. Lage, SCHEMA Consortium.


Thursday, October 17

4:15 PM–5:15 PM

Concurrent Platform Session E

62. Haplotype-level Interrogation of the Genome

Room 310A, Level 3, Convention Center

Moderators: Avery Davis Bell, Harvard Med Sch, Boston
  Joanna Kaplanis, Wellcome Sanger Inst, Hinxton, UK

 

220/4:15 PRINCESS: Framework for comprehensive detection and phasing of SNPs and SVs. M. Mahmoud, F.J. Sedlazeck.

221/4:30 A robust and production-level approach to haplotype-resolved assembly of single individuals. S. Garg, C. Fungtammasan, A. Carroll, R. Hall, E. Hatas, M. Mahmoud, F. Sedlazeck, M. Chou, J. Aach, J. Zook, J. Chin, G. Church.

222/4:45 Interrogating and correcting fine-scale genetic structure in large (>36,000 samples) GWAS datasets using scalable haplotype sharing methods. R.P. Byrne, W. van Rheenen, J.H. Veldink, R.L. McLaughlin.

223/5:00 Long-read single molecule, real-time (SMRT) sequencing of NUDT15: Phased full gene haplotyping and pharmacogenomic allele discovery. Y. Yang, M.R. Botton, E.R. Scott, Y. Seki, J. Harting, P. Baybayan, N. Cody, P. Nicoletti, T. Moriyama, T. Lin, S. Chakraborty, J.J. Yang, L. Edelmann, E.E. Schadt, J. Korlach, S.A. Scott.


Thursday, October 17

4:15 PM–5:15 PM

Concurrent Platform Session E

63. RNAseq to Augment Variant Interpretation and Disease Diagnosis

Room 360D, Level 3, Convention Center

Moderators: Erica Davis, Duke Univ, Durham
  Benjamin Kang, Emory Univ, Atlanta

 

224/4:15 Diagnostic utility of transcriptome sequencing for rare Mendelian diseases. H. Lee, A.Y. Huang, L. Wang, A.J. Yoon, G. Renteria, R.H. Signer, S. Nieves-Rodriguez, C.G.S. Palmer, J.A. Martinez-Agosto, S.F. Nelson, Undiagnosed Diseases Network.

2456/4:30 RNASeq enhances detection rates of exome sequencing of myocardial tissue from heart transplant patients with dilated cardiomyopathy. S. Amr, E. Park, M. Bowser, R. Waikel, M. Guglin, K. Campbell, A. Psychogios.

226/4:45 Characterization of human-derived transdifferentiated neurons for assessing splicing and allele expression in undiagnosed neurodevelopmental and neurological disorders. S. Nieves-Rodriguez, F. Barthelemy, J. Wan, A. Huang, L. Wang, H. Lee, M.C. Miceli, S.F. Nelson.

227/5:00 FRASER: A statistical method to detect aberrant splicing events in RNA-seq data. C. Mertes, I. Scheller, V.A. Yépez, Y. Liang, F. Brechtmann, H. Prokisch, J. Gagneur.


Thursday, October 17

4:15 PM–5:15 PM

Concurrent Platform Session E

64. Genetic Basis of Diabetes

Room 361D, Level 3, Convention Center

Moderators: Kerrin Small, King's Col London, UK
  Xueling Sim, Natl Univ Singapore

 

228/4:15 Discovery of 310 novel loci for type-2 diabetes and related complications involving 1.4 million participants in a multi-ethnic meta-analysis. M. Vujkovic, J. Keaton, J.A. Lynch, D. Miller, J. Zhou, S. Damrauer, T. Assimes, Y.V. Sun, T. Edwards, K. Cho, S. Duvall, P. Wilson, D.J. Rader, C.J. O'Donnell, J. Meigs, J.M. Gaziano, P.S. Tsao, L. Phillips, P. Reaven, K.M. Chang, B.F. Voight, D. Saleheen, on behalf of the Million Veteran Program.

229/4:30 The high prevalence of pathogenic mutations in genes causing monogenic diabetes in patients with common type 2 diabetes opens avenues towards precision medicine. P. Froguel, M. Boissel, E. Durand, B. Toussaint, E. Vaillant, S. Gaget, R. Roussel, B. Balkau, M. Marre, S. Franc, G. Charpentier, M. Vaxaillaire, M. Canouil, A. Bonnefond.

230/4:45 Chromatin accessibility patterns of a hiPSC model of islet development highlight type 2 diabetes risk loci in beta cell differentiation. M. Pérez Alcántara, M. Jansen, M. Thurner, A.L. Gloyn, A. Mahajan, A. Wesolowska-Andersen, M.I. McCarthy.

231/5:00 Identifying mechanisms of type 1 diabetes risk by integrating genetic fine-mapping, high-throughput transcription factor binding and chromatin accessibility. P. Benaglio, J. Chiou, S. Corban, M. Okino, A. Aylward, J. Yan, N. Nariai, B. Ren, K. Frazer, K. Gaulton.


Thursday, October 17

4:15 PM–5:15 PM

Concurrent Platform Session E

65. Grim Inheritance: Germline Predisposition to Pediatric and Adult Cancers

Room 370A, Level 3, Convention Center

Moderators: Gordana Raca, Children's Hosp Los Angeles
  Honey Reddi, The Jackson Laboratory

 

232/4:15 Frequency of pathogenic germline variation in pediatric pan-cancer survivors: A report from the Childhood Cancer Survivor Study (CCSS). D.M. Gianferante, J. Kim, D. Karyadi, S. Hartley, M. Frone, L. Robinson, G. Armstrong, S. Bhatia, M. Dean, M. Yeager, B. Zhu, L. Song, S. Brodie, K. de Andrade, K. Santiago, A. Goldstein, P. Khincha, M. Machiela, M. McMaster, M. Nickerson, L. Oba, A. Pemov, M. Pinheiro, M. Rotunno, M. Tucker, L. Morton, S. Chanock, S. Savage, D. Stewart, L. Mirabello, NCI-DCEG Cancer Genomics Research Laboratory.

233/4:30 Evaluating the prevalence of pathogenic variants in cancer predisposition genes among children with newly diagnosed rhabdomyosarcoma: A report from the Children’s Oncology Group. H. Li, S.D. Sisoudiya, D.S. Hawkins, G.C. Kendall, J.F. Amatruda, S.X. Skapek, S. Dugan-Perez, D.A. Marquez-Do, M.E. Scheurer, D. Muzny, R.A. Gibbs, S.E. Plon, P.J. Lupo, A. Sabo.

234/4:45 The Healthy Oregon Project: Initial laboratory findings for inherited cancer predisposition screening in a large population in the Pacific Northwest. T.D. O'Brien, A.B. Potter, A. Kulkarni, G. Goh, J.H. Letaw, C.S. Dahl, J. Pleyte, J. Thanner, T.J. McFarland, S. Medica, C.A. Harrington, K.J. Hamman, J. Sampson, K. Johnson-Camacho, J. Shannon, P.T. Spellman, C.S. Richards.

235/5:00 Limitations of direct-to-consumer genetic screening for hereditary breast, ovarian, and colorectal cancer risk. E.D. Esplin, E. Haverfield, S. Yang, B. Herrera, M. Anderson, R. Nussbaum.


Thursday, October 17

4:15 PM–5:15 PM

Concurrent Platform Session E

66. Heritability and Dominance in Complex Traits

Room 371A, Level 3, Convention Center

Moderators: Stephen Rich, Univ Virginia, Charlottesville
  Cristina Justice, NHGRI, Baltimore

 

236/4:15 Functionally-informed fine-mapping improves polygenic localization of complex trait heritability. F. Hormozdiari, O. Weissbrod, C. Benner, R. Cui, J. Ulirsch, A. Schoech, S. Gazal, Y. Reshef, B. Geijn, C. Márquez-Luna, L. O’Connor, H. Finucane, A. Price.

237/4:30 Estimating heritability and its enrichment in tissue-specific gene sets in admixed populations. X. Li, Y. Luo, X. Wang, S. Gazal, J.M. Mercader, B.M. Neale, J.C. Florez, A. Auton, A.L. Price, H.K. Finucane, S. Raychaudhuri, 23andMe Research Team, SIGMA Type 2 Diabetes Consortium.

238/4:45 Efficient variance components analysis across millions of genomes. A. Pazokitoroudi, Y. Wu, K. S. Burch, K. Hou, A. Zhou, B. Pasaniuc, S. Sankararaman.

239/5:00 The role of dominance in complex traits in the UK Biobank. D.S. Palmer, W. Zhou, A. Bloemendal, L. Abbott, N.A. Baya, B.M. Neale.


Thursday, October 17

5:30 PM–7:00 PM

67. Presidential Symposium: Genetic Exceptionalism - From Its Beginning to Its End?

Hall B, Level 1, Convention Center

Moderator: Leslie G. Biesecker, ASHG 2019 President

 

This symposium will focus on several areas of genetic exceptionalism. The speakers will discuss the topic from its origins and history to how it affects everyday practice of genetics. The thesis of this symposium is that exceptionalism is a barrier to the vision of the Society, which is that "People everywhere realize the benefits of human genetics and genomics research." Exceptionalism creates barriers in academia between geneticists and other scientists. It isolates geneticists from other specialists and providers in hospitals and clinics. This barrier must be broken down to realize these benefits. To address this challenge, we have assembled three distinguished lecturers, who will puncture the exceptionalism balloon. The symposium will close with a moderated panel discussion to discuss how we move forward.

 

5:30 PM   How genetics got its exceptionalism. R. Resta, MS, CGC. Swedish Hosp, Seattle.

5:55 PM   Behavioral impact of predictive testing: The unexceptional contribution of genetic information. D. Marteau, PhD, DBE. Univ Cambridge, UK.

6:20 PM   The everyday reality of genetics in the clinic: It's just medicine. K. Brothers, MD, PhD. Univ Louisville.

6:45 PM   Panel discussion.


Friday, October 18

9:00 AM–10:00 AM

Concurrent Platform Session F

68. Transferability of Polygenic Risk Scores Across Populations

Hall B, Level 1, Convention Center

Moderators: Brooke Wolford, Univ Michigan, Ann Arbor
  Elizabeth Blue, Univ Washington, Seattle

 

240/9:00 Characterizing portability of complex trait associations across the diverse populations of the PAGE Study. C. Gignoux, M. Graff, S. Bien, R. Tao, J. Haessler, H. Highland, Y. Patel, L. Hindorff, S. Buyske, C. Haiman, L. Le Marchand, R. Loos, T. Matise, U. Peters, K. North, C. Avery, C. Kooperberg, E. Kenny, G. Wojcik, The PAGE Study.

241/9:15 Application of European-derived polygenic risk score to admixed populations reveals strong biases by ancestry. G. Wojcik, S.A. Bien, M. Graff, C.L. Avery, S. Buyske, C. Haiman, L. Le Marchand, C. Kooperberg, R.J.F. Loos, T.C. Matise, K.E. North, U. Peters, S.S. Rich, C.R. Gignoux, C.D. Bustamante, E.E. Kenny.

242/9:30 The role of linkage disequilibrium structure in transferability of polygenic risk scores. P. Orozco del Pino, S. Zöellner.

243/9:45 Investigating the lack of transferability of polygenic risk scores in cohorts with admixed ancestry. B. Domingues Bitarello, I. Mathieson.


Friday, October 18

9:00 AM–10:00 AM

Concurrent Platform Session F

69. Tangled Webs: Deconstructing Complex Regulatory Networks in Cancer

Grand Ballroom A, Level 3, Convention Center

Moderators: Ken Chen, MD Anderson Cancer Cent, Houston
  Semanti Mukherjee, Memorial Sloan Kettering Cancer Cent, New York

 

244/9:00 Multi-omic analysis maps the genomic landscape of ovarian cancer to reveal mutational mechanisms and functional pathways that drive chemoresistance. M.R. Jones, S.G. Coetzee, N.M. Gull, K. Dabke, C.A. Kalita, A.L.P. Reyes, J.T. Plummer, B.D. Davis, S. Chen, J.P.B. Govindavari, J. Lester, K. Lawrenson, D. Hazelett, A. Gusev, S. Parker, B.P. Berman, B. Karlan, S.A. Gayther.

245/9:15 Prediagnostic serum RNA levels are highly dynamic in lung cancer. R. Lyle, S. Umu, H. Langseth, A. Keller, E. Meese, A. Helland, T. Rounge.

246/9:30 Iterative deconvolution around a single gene allows improved accuracy in comparing MSLN high and low PDAC tumors. E. LaPlante, E. Lurie, D. Liu, Q. Yao, A. Milosavljevic.

247/9:45 Network-based identification of key master regulators for immunologic constant of rejection in cancer. R. Mall, M. Saad, J. Rolands, W. Hendrickx, M. Ceccarelli, D. Bedgonetti.


Friday, October 18

9:00 AM–10:00 AM

Concurrent Platform Session F

70. Fast Methods for Genome Analysis

Grand Ballroom B, Level 3, Convention Center

Moderators: Liliana Florea, Johns Hopkins Univ Sch Medicine, Baltimore
  Brittany Lasseigne, Univ Alabama Birmingham

 

248/9:00 Assembling a de novo human genome in 100 minutes. A. Khalak, C.-S. Chin.

249/9:15 RaPID: An ultra-fast method for identifying IBDs in biobanks. D. Zhi, X. Liu, K. Tang, S. Zhang, A. Naseri.

250/9:30 Efficient approximation of GWAS resampling for method validation on massive datasets. N.A. Baya, R.K. Walters, J. Bloom, B.M. Neale.

251/9:45 An artificial intelligence approach for nearly instant diagnosis of Mendelian diseases by deep phenotyping and whole-genome or exome sequencing. M. Yandell, M. Falconi, B. Moore, S. Nohzadeh-Malakshah, E. Frise, E. Kiruluta, M. Reese, F. De La Vega.


Friday, October 18

9:00 AM–10:00 AM

Concurrent Platform Session F

71. Use of Single Cell RNA-seq to Dissect Fundamental Cellular Processes

Grand Ballroom C, Level 3, Convention Center

Moderators: Chelsea Raulerson, Univ North Carolina Chapel Hill
  Carol Bult, Jackson Lab, Bar Harbor

 

252/9:00 Single-cell transcriptomics reconstructs developmental tree from embryonic stem cell to insulin producing cells. C. Weng, J. Xi, H. Li, Y. Li, F. Jin.

253/9:15 Characterizing cellular communication in human central nervous system by single-cell RNA sequencing. Z. Miao, G. Hu, K. Wang, A. Nguyen, Y. Lyu, J. Lakkis, C. Strang, C. Curcio, D. Stambolian, E. Lee, M. Li.

254/9:30 Reconstructing pseudotemporal trajectories in single-cell RNA-seq data using neural networks. J. Lakkis, G. Hu, H. Zhang, C. Xue, M. Reilly, M. Li.

255/9:45 Integrative single-cell and bulk RNA-seq analysis in human retina identified cell type-specific composition and gene expression changes for age-related macular degeneration. Y. Lyu, R. Zauhar, N. Dana, C. Strang, K. Wang, Z. Miao, P. Gamlin, C. Curcio, D. Stambolian, M. Li.


Friday, October 18

9:00 AM–10:00 AM

Concurrent Platform Session F

72. Integrated Genomics and Transcriptomics in Parkinson's Disease

Room 310A, Level 3, Convention Center

Moderators: Paul C. Marcogliese, Baylor Col Med, Houston
  Yi-Ju Li, Duke Univ Med Cent, Durham

 

256/9:00 Identifying the role of genetics and neurodevelopment in sporadic late onset Parkinson’s disease. S. Kumar, J.E. Curran, J.M. Peralta, A.C. Leandro, D.M. Lehman, D.C. Glahn, J. Blangero.

257/9:15 Parkinson's disease derived monocytes show alteration in the phago-lysosomal pathway. E. Udine, E. Navarro, M. Parks, G. Riboldi, K. Lopes, B. Schilder, T. Sikder, K. Watkins, M. Zhang, D. Raymond, S. Elango, E. Wieder, S. Simon, S. Bressman, J. Crary, S. Frucht, R. Saunders-Pullman, T. Raj.

258/9:30 Compound heterozygous mutations in ATP10B compromising lysosomal glucosylceramide flippase activity are associated with Parkinson’s disease. S. Smolders, S. Martin, C. Van den Haute, B. Heeman, S. van Veen, D. Crosiers, I. Beletchi, A. Verstraeten, G. Gelders, P. Pals, N. Hamouda, S. Engelborghs, J.J. Martin, J. Eggermont, P.P. De Deyn, P. Cras, V. Baekelandt, P. Vangheluwe, C. Van Broeckhoven, the BELNEU consortium.

259/9:45 An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of a-synuclein. E. Kara, A. Crimi, M. Emmenegger, C. Manzoni, S. Bandres Ciga, J. Botia, A. Wiedmer, M. Carta, D. Heinzer, M. Avar, A. Chincisan, C. Blauwendraat, S. Garcia Ruiz, D. Pease, L. Mottier, A. Carrella, D. Schneider, A. Magalhaes, C. Aemisegger, Z. Fan, J. Marks, S. Hopp, P. Lewis, M. Nalls, M. Ryten, J. Hardy, B. Hyman, A. Aguzzi.


Friday, October 18

9:00 AM–10:00 AM

Concurrent Platform Session F

73. Alternative Methods for Evaluating Variant Pathogenicity

Room 360D, Level 3, Convention Center

Moderators: Jessica Chong, Univ Washington, Seattle
  Peter Robinson, Jackson Lab Genomic Med, Farmington

 

260/9:00 Titin, the most challenging human gene, requires a multidisciplinary extensive approach. M. Savarese, M. Johari, A. Vihola, P.H. Jonson, H. Luque, T. Qureshi, S. Välipakka, S. Koivunen, M. Arumilli, J. Sarparanta, P. Hackman, B. Udd.

261/9:15 Protein function-specific structural insights into the effect of Mendelian disease variants in 1,330 human genes. S. Iqbal, E. Perez-Palma, J. Jespersen, P. May, D. Hoksza, H. Heyne, S. Ahmed, Z. Rifat, S. Rahman, K. Lage, A. Palotie, J. Cottrell, F. Wagner, M. Daly, A. Campbell, D. Lal.

262/9:30 NOTCH3 cysteine altering variants among the 92,456 whole exome sequenced participants of the Geisinger DiscovEHR initiative. R.J. Hack, N. Pearson, J.W. Rutten, J. Li, A. Khan, M.A. Iqbal, J. Hornak, V. Abedi, Y. Zhang, M.T.M. Lee, C. Griessenauer, . Regeneron Genetics Center, S.A.J. Lesnik Oberstein, R. Zand.

263/9:45 Identification of functionally essential sites using 3D single protein and multiprotein complexes across 73 neurodevelopmental disorder-associated genes. T. Brünger, S. Iqbal, E. Perez-Palma, M.J. Daly, A.J. Campbell, P. May, D. Lal.


Friday, October 18

9:00 AM–10:00 AM

Concurrent Platform Session F

74. Detection and Evaluation of Actionable Findings: ACMG 59 and Beyond

Room 361D, Level 3, Convention Center

Moderators: Laura Amendola, Univ Washington Med, Seattle
  Katrina Goddard, Kaiser Permanente Cent Hlth Res, Portland

 

264/9:00 Million Veteran Program Return Of Actionable Results - Familial Hypercholesterolemia (MVP-ROAR-FH) Study: Considerations for variant return to mega-biobank participants. J.L. Vassy, N. Alexander, T. Assimes, C.A. Brunette, T.E. Callis, K.D. Christensen, M. Danowski, Q. Hui, J.W. Knowles, V.A. Morrison, A.C. Sturm, Y. Sun, M. Vatta, V.L. Venne, for the MVP-ROAR-FH Study.

265/9:15 Comprehensive secondary findings analysis of parental samples submitted for exome evaluation yields a high positive rate. E.V. Haverfield, E.D. Esplin, S. Aguilar, S. Yang, R. Truty, R.L. Nussbaum, S. Aradhya.

266/9:30 Secondary inherited cardiac condition findings from genome sequencing: Variant interpretation, assessment of phenotype, and impacts of disclosure. A.R. Harper, K. Thomson, M. Mackley, H. Watkins, E. Ormondroyd.

267/9:45 Secondary findings in non-ACMG 59™ genes. A.E. Katz, J. Paschall, H. Shiferaw, X. Liu, W.S.W. Wong, T.P. Conrads, G.L. Maxwell, D.P. Ascher, L.G. Biesecker, The Genomic Ascertainment Cohort (TGAC).


Friday, October 18

9:00 AM–10:00 AM

Concurrent Platform Session F

75. Reproductive Fitness: Genetic Insights into Fertility

Room 370A, Level 3, Convention Center

Moderators: Rajiv McCoy, Johns Hopkins Univ, Baltimore
  Li Lu, Baylor Genetics, Houston

 

268/9:00 Expanded CGG repeat RNA and FMRpolyG in the oocyte leads to impaired response to gonadotropin hormones in a murine model of the FMR1 premutation. K. Shelly, N. Candelaria, Z. Li, P. Jin, D. Nelson.

269/9:15 Exome sequencing reveals de novo mutations and deletions in severe unexplained male infertility. M. Oud, R.M. Smits, F.K. Mastrorosa, H. Smith, M.J. Xavier, G.S. Holt, H. Sheth, B.J. Houston, T. Luan, R. Burke, M.K. O'Bryan, P.F. de Vries, B. Alobaidi, H. Ismail, A. Garcia-Rodriguez, A. Mikulasova, G. Astuti, C. Gilissen, L.E.L.M. Vissers, C. Friedrich, F. Tuttelmann, K. McEleny, J. Coxhead, S. Cockell, D.D.M. Braat, K. Fleischer, G.W. van der Heijden, L. Ramos, J.A. Veltman.

270/9:30 Aneuploidy and recombination across chromosomes, gametes, and individuals from large-scale single-sperm sequencing. A.D. Bell, C.J. Mello, J. Nemesh, S.A. Brumbaugh, A. Wysoker, A. Leung, D. Sakkas, S.A. McCarroll.

271/9:45 Disruption of genes essential for Müllerian duct/Wolffian duct development in Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS). N. Wu, N. Chen, S. Zhao, H. Pan, L. Wang, A. Jolly, Z. Wu, P. Liu, J. Posey, J. Lupski, L. Zhu.


Friday, October 18

9:00 AM–10:00 AM

Concurrent Platform Session F

76. Sex Differences in Genetic Disorders

Room 371A, Level 3, Convention Center

Moderators: Eric Vilian, Children's Natl Hlth Sys, Washington, D.C.
  Carole Samango-Sprouse, George Washington Univ, Washington, D.C.

 

272/9:00 Sexual dimorphism in genetic associations of testosterone and sex-hormone binding globulin with cardiometabolic diseases. J. Hu, J. Li, K.M. Rexrode, L. Liang.

273/9:15 A sex-stratified meta-analysis of 537,602 individuals identifies sex-specific effects on susceptibility to inguinal hernia. E. Jorgenson, J. Yin, A. Sohota, R. Mostaedi, N. Ahituv, H. Choquet.

274/9:30 Sex-biased gene expression in fetal brain is distinct from adult brain and gives new insights on neurodevelopmental disorders. C. Benoit-Pilven, J. Leinonen, J. Karjalainen, M. Daly, T. Tukiainen.

275/9:45 Sex-dependent glia-specific changes in the epigenome landscape of the APOE region in Alzheimer’s disease brains. O. Chiba-Falek, L. Song, J. Barrera, A. Safi, Y. Jun, M. Garrett, A. Ashley-Koch, G. Crawford.


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

77. Unraveling the Mysteries of Mosaicism: Implications for Biology and Disease

Hall B, Level 1, Convention Center

Moderator: Nancy B. Spinner, Children's Hosp Philadelphia

 

The human body is composed of approximately 40 trillion cells, derived from a single zygote, yet no two cells are genetically identical. The study of mosaicism has benefited from advances in genomic technology to begin to capture some of this incredible genomic diversity across organs and cell types and to understand the impact on genomic health and disease. This is due not only to dropping sequencing costs, but also to the fact that individual "reads" derive from distinct DNA molecules or cells, enabling both bulk-sequencing and single-cell-sequencing assessment of mosaicism. This session will highlight how post-zygotic mutations, revealed through the study of mosaicism, have advanced our understanding of cell lineage, cell proliferation, responses to drugs, and gene-gene interactions, as well as how they impact human health. The speakers will discuss: (1) how clonal hematopoiesis can influence age-associated disease, (2) how clonal hematopoiesis of indeterminate potential (CHIP) is detected and interpreted in the context of hematological malignancies and response to anti-cancer therapies, (3) how brain somatic mosaicism can be used to understand cellular origins and disease, (4) how somatic pathogenic variants and revertants that rescue germline pathogenic variants influence disease, and (5) how this information impacts both clinical and research geneticists.

 

10:30 AM   Clonal hematopoiesis and its impact on age-associated disease. K. Walsh. Univ Virginia, Charlottesville.

11:00 AM   Impact of oncologic therapy on clonal hematopoiesis and therapy-related myeloid neoplasm in solid tumor patients. K. Bolton. Memorial Sloan Kettering Cancer Ctr, New York.

11:30 AM   One brain, many genomes: Somatic mutation and genomic diversity in human brain. C.A. Walsh. Boston Children's Hospital.

12:00 PM   Genetic analysis of cutaneous mosaic disorders reveals novel pathways for disease pathogenesis and therapy. K. Choate. Yale Univ, New Haven.


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

78. Clinical Spotlight: Basic Research to Clinical Implementation: A Multidisciplinary Overview of the Current State and Future Directions of Clinical Pharmacogenomic Testing

Grand Ballroom B, Level 3, Convention Center

Moderators: Ulrich Broeckel, Med Col Wisconsin, Milwaukee
  Mary V. Relling, St. Jude Children's Hosp, Memphis

 

This is a multidisciplinary discussion of the current progress and challenges in implementing pharmacogenomic diagnostic testing as part of genomics-guided precision medicine. This session will include updates on the current status and future direction of nomenclature standardization, the role of health professionals in diagnostic implementation, and the translation of basic science from the bench to the clinic. Our session will include talks from a range of scientists and healthcare providers. The interactive panel discussion will allow for audience questions on pharmacogenomic research and clinical implementation. Attendees will be able to ask questions and get insight from a range of healthcare professionals and discuss the need for and different roles in multidisciplinary collaboration for clinical implementation.

 

10:30 AM   From discovery science to clinical implementation: A case study of NUDT15 and thiopurine pharmacogenomics. J.J. Yang. St. Jude Children's Res Hosp, Memphis.

10:55 AM   The Pharmacogene Variation (PharmVar) Consortium: What you need to know. A. Gaedigk. Children's Mercy Kansas City.

11:20 AM   Genetic counselors role and perspective in pharmacogenomics, reimbursement, and provider preferences for result reports. C.A. Campbell. Univ Iowa, Iowa City.

11:45 AM   Pharmacist perspective on pharmacogenomic implementation. D. Gregornik. Children's Hosp Minnesota, Minneapolis.

12:10 PM   Panel discussion.


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

79. Cutting-edge Approaches to Interrogating the Genomics of Infectious Disease

Grand Ballroom C, Level 3, Convention Center

Moderators: Genevieve Wojcik, Stanford Univ Sch Med
  Priya Duggal, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore

 

Throughout human history, infectious pathogens have exerted enormous selective pressure on our genomes. Infectious disease continues to contribute substantially to global morbidity and mortality, despite remarkable advancements in hygiene and vaccination over the past century. However, infectious disease susceptibility and sequelae are underrepresented in large-scale genomic research even though there is a clear role for genetics. Various studies have shown high heritability of our immune system’s response to antigens, such as the antibody response to measles vaccination at 88.5%. This lack of preeminence is due to several challenges, including the underrepresentation of populations with the highest burden of disease, the difficulty in appropriate comparison groups, the time-sensitive nature of recruitment, and, lastly, the incomplete picture from traditional study designs, where we only assess a small portion of complex host-pathogen genetic interactions. This session will showcase groundbreaking work by four researchers to tackle these challenges and interrogate the dynamic genetic system of host-pathogen interactions. This will include perspectives from real-time recruitment of an infectious disease outbreak, evolutionary analyses examining human and pathogen diversity, community-driven research in Sub-Saharan Africa, and the creation of an atlas of genetic variation for pathogen-driven cellular traits.

 

10:30 AM   What are the challenges and benefits in studying the genetics of infectious diseases? P. Duggal. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore.

11:00 AM   Importance of epidemiological study design in genetic studies of tuberculosis. C. Stein. Case Western Reserve Univ, Cleveland.

11:30 AM   Natural selection contributed to immunological differences between human hunter gatherers and agriculturalists. G. Harrison. Univ Colorado, Anschutz Med Campus, Aurora.

12:00 PM   An atlas of human genetic variation affecting host-pathogen traits. D. Ko. Duke Univ, Durham.


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

80. Novel Biomarkers and Emerging Therapeutic Approaches in Mitochondrial Disorders

Room 361D, Level 3, Convention Center

Moderators: Fernando Scaglia, Baylor Col Med, Houston
  Amel Karaa, Massachusetts Gen Hosp/Harvard Univ, Cambridge

 

Recent data from disease models highlight whole-organism metabolic remodeling in mitochondrial disorders. Furthermore, these dysfunctional metabolic pathways may be amenable to therapeutic approaches. Although the metabolomics aberrations in mitochondrial disorders have not been completely dissected, some preliminary work has found evidence of disease-specific metabolomics signatures in the blood and tissues of patients with primary mitochondrial disorders. This suggests the potential of metabolomics fingerprints as biomarkers for diagnosis that could be used to follow-up disease progression and monitor potential therapeutic effects in clinical trials. Furthermore, this information could help to shed light into specific pathogenic pathways. Many potential therapeutic approaches for mitochondrial diseases have been proposed and are now at different stages of development. Translating preclinical studies to the bedside remains challenging, and well-controlled trials of high quality are necessary to define the efficacy of potential therapies already in use and to develop novel drugs. Based on the knowledge acquired with previous studies, these future trials may overcome the challenges posed by this heterogeneous group of disorders in the context of multicenter collaborations by selecting numerous subgroups of homogeneous patients and outcome measures that are objective and relevant to patient care and quality of life. The emerging therapies provide exciting promise for clinically meaningful treatments for mitochondrial diseases. This session will highlight the prospects of using an untargeted metabolomics approach to evaluate disease progression and therapeutic interventions in mitochondrial disease and will discuss some of the emergent therapeutic approaches.

 

10:30 AM   Untargeted metabolomic profiling in mitochondrial disease: Emerging biomarkers. S.H. Elsea. Baylor Col Med, Houston.

11:00 AM   Nucleoside bypass therapy for mitochondrial disorders. M. Hirano. Columbia Univ Med Ctr, New York.

11:30 AM   Mitochondrial replacement therapy. S. Mitalipov. Oregon Hlth Sci Univ, Portland.

12:00 PM   Hypoxia as a potential therapeutic approach for mitochondrial disorders. V.K. Mootha. Massachusetts Gen Hosp, Boston.


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

81. Poison Exons in Neurodevelopmental Disorders: From Development and Disease to Therapeutic Target

Room 310A, Level 3, Convention Center

Moderators: Gemma L. Carvill, Northwestern Univ, Chicago
  Heather C. Mefford, Univ Washington, Seattle

 

This session will focus on the role of poison exons in epilepsy. Poison exons are small exonic regions that, when spliced into an RNA transcript, lead to premature truncation of a protein. Inclusion of poison exons occurs during specific times in neurodevelopment, and splicing occurs in a cell-specific manner. Many of the genes implicated in neurodevelopmental disorders, including epilepsy, autism, and malformations of cortical development, harbor these poison exons. These include ion channels (SCN1A/2A/8A), epigenetic regulators (CHD2, MBD5), and cytoskeletal proteins (FLNA). In this session, Dr. Mefford will open by describing the current genetic landscape of neurodevelopmental disorders and strategies to identify the molecular etiology in undiagnosed cases. Dr. Mefford will also introduce the concept of poison exons and their function. Dr. Zhang will discuss the studies that identified poison exons in neuronal development, the splicing mechanisms that govern their use, and variants detected in patients with malformations of cortical development that disrupt their splicing. Dr. Carvill will discuss the identification of patient-specific variants that lead to aberrant inclusion of poison exons in genes implicated in epilepsy, including SCN1A, and functional studies in patient-derived induced neurons. Dr. Isom will describe an antisense oligonucleotide that targets an SCN1A poison exon, preventing its inclusion and thus restoring full-length protein and preventing SCN1A-related mortality in an animal model of epilepsy.

 

10:30 AM   A role for poison exons in neurodevelopmental disorders. H.C. Mefford. Univ Washington, Seattle.

11:00 AM   Alternative splicing of poison exons during human neuronal development. X. Zhang. Univ Chicago.

11:30 AM   Aberrant inclusion of poison exons leads to premature truncation of ion channels in epilepsy. G.L. Carvill. Northwestern Univ, Chicago.

12:00 PM   Rescuing SCN1A haploinsufficiency using an antisense oligonucleotide (ASO) targeting a poison exon in a genetic model of epilepsy. L. Isom. Univ Michigan, Ann Arbor.


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

82. The Intersection of Genetics and the Disability Rights Movement: Beginning a Dialogue about the Impact of Prenatal Genetic Screening and Testing on Historically Stigmatized Populations

Room 360D, Level 3, Convention Center

Moderators: Marsha Michie, Case Western Reserve Univ, Cleveland
  Katie Stoll, Genet Support Fndn, Olympia

 

With the expansion of prenatal screening and testing, an increasing number of fetuses are being identified as having genetic variants that can lead to different disabilities. Many of these genetic conditions entail serious health and cognitive issues. However, in a society where people with disabilities have been historically stigmatized through segregation and institutionalization, a genetic diagnosis can also lead to fears and misperceptions based on social biases, particularly when patients are not provided information or support to explain the social context of disability. Traditionally, the medical model of disability has focused on the health issues associated with various genetic conditions; however, research shows that patients also want information about evolving life outcomes and available support and services. Unfortunately, research also shows that many patients are not provided the information and support they need to understand prenatally-diagnosed conditions in a social context. Toward that end, a bioethicist/anthropologist and a public policy expert will moderate a panel of interdisciplinary experts, including a disability studies scholar/clinical psychologist, a geneticist, a clinician, and a patient education expert. The panel will present on the impact of genetic testing on social biases toward people with disabilities, the current implementation of screening and testing, and the current status of the patient support and educational infrastructure. The session will conclude with a robust discussion with the audience about ways geneticists, disability rights scholars, clinicians, and public health policy experts can unite to create deliberate strategies to ensure the equitable representation of the disability rights movement in the genetics field.

 

10:30 AM   Introduction. M. Michie. Case Western Reserve Univ, Cleveland.

10:40 AM   Exploring the roles of implicit bias and attitudes about disability in navigating ethically complex decisions related to prenatal genetic diagnostic testing. K. Ayers. Univ Cincinnati.

10:55 AM   On the intersection of disability identity and advances in IDD science. J. Constantino. Washington Univ Sch Med St Louis.

11:10 AM   An exploration of strategies for merging the social and medical models of disabilities among clinicians and professional societies in an era of expanded prenatal screening and testing. I. Van den Veyver. Baylor Col Med, Houston.

11:25 AM   Addressing the disability rights movement in the practice of genomic medicine through accurate, balanced, and up-to-date patient education strategies. S. Meredith. Univ Kentucky, Lexington.

11:40 AM   Synthesis and introduction to panel. K. Stoll. Genet Support Fndn, Olympia.

11:50 AM   Panel discussion.


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

83. The New Frontier of Epigenetics in Cancer: Modifications of Nucleic Acids

Grand Ballroom A, Level 3, Convention Center

Moderators: Tao P. Wu, Baylor Col Med, Houston
  Yun Huang, Texas A&M, Houston

 

In the last ten years, dramatic advances in sequencing and high-sensitivity analytical technologies have fundamentally changed the field of human molecular genetics research, particularly in cancer diagnosis and treatment. Although human cancer can be driven by the accumulation of genetic mutations, it can also be driven by non-genetic factors such as dysregulation of metabolic pathways or alterations of epigenetic regulatory processes. In this session, we will showcase the extraordinary impact that the abnormal DNA/RNA modifications ("epi-mutations") are making on tumorigenesis. First, Andrew Xiao, will present how a novel DNA methylation (6mA) was discovered in mammals and its function in glioblastoma. Next, Daniel De Carvalho will describe how his novel approach of cfDNA methylation analyses can detect cancer earlier with a blood test. The third speaker, Yun Huang, will present on the role of TET-mediated DNA methylcytosine oxidation in development. Finally, Anjana Rao will show how the novel modifications of cytosine were discovered and present the critical contributions of these modifications to the neoplastic progress. Her research uncovers a new direction for human disease diagnosis and treatment.

 

10:30 AM   Novel DNA methylation N6-mA in mammals. A. Xiao. Yale Univ, New Haven.

11:00 AM   Sensitive tumour detection and classification using plasma cell-free DNA methylomes. D. De Carvalho. Univ Toronto, Canada.

11:30 AM   Role of TET-mediated DNA methylcytosine oxidation in development. Y. Huang. Texas A&M, Houston.

12:00 PM   TET methylcytosine oxidases in cell differentiation, immune responses and cancer. A. Rao. La Jolla Inst for Immunology.


Friday, October 18

10:30 AM–12:30 PM

Concurrent Invited Session III

84. Tribal Colleges and Universities: Teaching Genomics with an Indigenous Perspective

Room 370A, Level 3, Convention Center

Moderators: Carla L. Easter, NHGRI, Bethesda
  Francis Onduso, Sitting Bull Col, Fort Yates

 

There are 32 accredited Tribal Colleges and Universities (TCUs) within the United States that serve approximately 30,000 students from more than 250 federally recognized American Indian and Alaska Native tribes. These colleges are chartered by their respective tribal governments, offer degree programs from the humanities to the sciences, and are in service to their respective communities. At the core of tribal colleges is providing quality and supportive higher education opportunities to predominantly American Indian students that are culturally and traditionally based. This session will discuss the importance of teaching genomics at tribal colleges and the various ways that tribal colleges are teaching genetics and genomics with an Indigenous perspective. Specific conversations also will focus on the importance of tribal college faculty and student networks in the field of genomics and the need for increased opportunities for conversations about the ethical, legal, and cultural concerns surrounding genomics for many American Indians and Alaska Natives.

 

10:30 AM   The inclusion of handheld DNA sequencers in classrooms at tribal colleges. R. Arnold. Northwest Indian Col, Bellingham.

11:00 AM   Developing culturally-inclusive genomics education at tribal colleges. K. Tsosie. Turtle Mountain Community Col, Belcourt.

11:30 AM   Tribal colleges consortium on genomics training. A. Quijada. Tribal Col Consortium Genomics Training, Tucson.

12:00 PM   Pursing a career in genomics for tribal college students. T. Vargas. Oglala Lakota Col, Kyle.


Friday, October 18

12:30 PM–1:30 PM

85. ASHG Membership Forum and Business Meeting

Room 320B, Level 3, Convention Center

Interact with ASHG Board members to discuss key society business activities, ASHG’s new Strategic Plan, and ways to get involved! Lunch will be provided to first 100 attendees.

 


Friday, October 18

3:30 PM–3:45 PM

86. ASHG Advocacy Award Presentation and Lecture: Positive Exposure: Celebrating the Beauty and Richness of Our Shared Humanity

Hall B, Level 1, Convention Center

Introduction: Jannine Cody, PhD, University of Texas Health Science Center

Rick Guidotti created the not-for-profit organization POSITIVE EXPOSURE, which uses visual arts to present the humanity and dignity of individuals living with genetic, physical, behavioral, and intellectual differences. The nonprofit celebrates the beauty and richness of human diversity.

Recipient

Rick Guidotti
Rick Guidotti, Positive Exposure

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

 


Friday, October 18

3:45 PM–4:00 PM

87. ASHG Mentorship Award Presentation and Lecture: Mentorship and the Joy of Paying it Forward

Hall B, Level 1, Convention Center

Introduction: Hans Bjornsson, MD, PhD, Johns Hopkins University

Hal Dietz, MD, has focused his research on understanding Marfan Syndrome and has dedicated significant time and effort to mentoring. Over the past 20 years, he has mentored over fifty successful mentees, who have gone on to obtain independent funding for their own research and received prestigious awards.

Recipient

Hal Dietz, MD,
Hal Dietz, MD, Johns Hopkins University School of Medicine

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.

 


Friday, October 18

4:00 PM–4:15 PM

88. ASHG Arno Motulsky-Barton Childs Award for Excellence in Human Genetics Education Presentation and Lecture: Fulfilling the Promise of Genomic Medicine: Interprofessional Collaboration, Educational Science, and a Global Community of Practice

Hall B, Level 1, Convention Center

Introduction: Kenneth Offit, MD, Memorial Sloan Kettering Cancer Center

Jeffrey Weitzel, MD; and Kathleen Blazer, EDD, MS, LCGC, have worked together to provide innovative and impactful cancer genomics education to clinicians and researchers from diverse training backgrounds and practice settings across the U.S. and internationally. Their NCI-funded CGEP initiatives have ranged from educating primary care physicians for referral-level competence, to preparing master’s and doctoral level clinicians for leadership in translational cancer genomics research.

Recipient

Jeffrey Weitzel, MD
Jeffrey Weitzel, MD, City of Hope Division of Clinical Cancer Genomics

Recipent

Kathleen Blazer, EDD, MS, LCGC
Kathleen Blazer, EDD, MS, LCGC, City of Hope Division of Clinical Cancer Genomics

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

 


Friday, October 18

4:15 PM–5:00 PM

89. Gruber Genetics Prize and Lecture: Cancer Driver Genes and Their Implications for Patients

Hall B, Level 1, Convention Center

Awarded annually by The Gruber Foundation, the Genetics Prize is presented to a leading scientist, or up to three, in recognition of groundbreaking contributions to any realm of genetics research. The recipient will receive a gold laureate pin and a $500,000 unrestricted cash award.

Recipient

Bert Vogelstein, MD
Bert Vogelstein, MD, Johns Hopkins University

Bert Vogelstein, MD, is being awarded for his discoveries of new genetic pathways and processes contributing to cancer. He showed that malignant transformation of colorectal cancers results from the stepwise acquisition of mutations in oncogenes and tumor suppressor genes, thus elucidating the somatic evolution of cancer. His work has advanced our understanding of cancer pathogenesis and led to the development of new diagnostic tests and targeted therapies for cancer.

 


Friday, October 18

5:15 PM–6:15 PM

90. Featured Plenary Abstract Session III

Hall B, Level 1, Convention Center

Moderators: Robert J. Klein, ASHG 2019 Program Committee
  Beryl B. Cummings, ASHG 2019 Program Committee

 

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

 

276/5:15 Large scale whole genome sequencing reveals the mutational and clonal landscape of the IBD colon. S. Olafsson, R. McIntyre, T. Coorens, P. Robinson, H. Lee-Six, M. Sanders, T. Butler, K. Arestang, C. Dawson, Y. Hooks, M.R. Stratton, I. Martincorena, M. Parkes, T. Raine, P.J. Campbell, C.A. Anderson.

277/5:35 Whole genome sequencing puts Cas9 off-target mutagenesis into the context of genetic drift. L.M.J. Nutter, S. Khalouei, J.D. Heaney, D.G. Lanza, S.M. Murray, K. Peterson, J.R. Seavitt, J.A. Wood, A. Ramani.

278/5:55 Using in vitro evolution to probe the genome-wide basis of chemotherapy resistance. M. Dow, J.C. Rodriguez, H. Carter, E. Winzeler.


Friday, October 18

6:15 PM–7:15 PM

91. Late-breaking Abstract Session

Hall B, Level 1, Convention Center

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.

 


Saturday, October 19

8:30 AM–9:30 AM

Concurrent Platform Session G : Non-CME

92. Genomics and Therapeutics of Cancer and Prevention

Hall B, Level 1, Convention Center

Moderators: Weiva Sieh, Icahn Sch Med Mount Sinai, New York
  Eduardo Vilar, MD Anderson Cancer Ctr, Houston

 

279/8:30 Driver fusions identified in 1,327 pediatric tumors and their implications in tumorigenesis and precision cancer care. F. Lin, L. Surrey, G. Wertheim, M. Luo, X. Zhao, K. Cao, R. Aplenc, R. Bagatell, A. Bauer, T. Bhatti, S. MacFarland, J. Maris, Y. Mosse, A. Resnick, M. Santi, P. Storm, S. Tasian, A. Waanders, S. Hunger, M. Li.

280/8:45 Drug repositioning opportunities for breast cancer prevention and treatment. G. Chenevix-Trench, J. Beesley, K. McCue, L. Fachal, M. Miranda, M. Spitzer, I. Dunham, A. Gaulton, A. Peters, I. Azani, G. Monteith, A. Antoniou, D.F.E. Easton, A. Dunning, F. AlEjeh, M. Ghoussaini, Breast Cancer Association Consortium and Consortium for Investigators of Modifiers of BRCA1/2.

281/9:00 Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer. Z. Khan, F. Di Nucci, A. Kwan, C. Hammer, S. Mariathasan, V. Rouilly, J. Carroll, M. Fontes, S. Ley Acosta, E. Guardino, H. Chen-Harris, T. Bhangale, J. Rosenberg, T. Powles, J. Hunkapiller, G.S. Chandler, M.L. Albert.

282/9:15 Multi-trait analysis of skin cancer and related traits identifies dozens of novel loci for cutaneous melanoma, including at CTLA-4 a key melanoma immunotherapy target. S. MacGregor, J. Shi, D.T. Bishop, E. Nagore, A.J. Stratigos, M.C. Fargnoli, P. Ghiorzo, K. Peris, A.E. Cust, J. Han, C. Olson, 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, K.M. Brown, D.C. Whiteman, M.T. Landi, M.M. Iles, M.H. Law.


Saturday, October 19

8:30 AM–9:30 AM

Concurrent Platform Session G : Non-CME

93. Bioinformatics and Machine Learning Methods

Grand Ballroom A, Level 3, Convention Center

Moderators: Fritz Sedlazeck, Baylor Col Med, Houston
  Sara Ballouz, Cold Spring Harbor Lab

 

283/8:30 mantis-ml: Stochastic semi-supervised learning to prioritise genes from high-throughput genomic screens. D. Vitsios, S. Petrovski.

284/8:45 After F-measure: Deep learning marginal variants from largest-scale cohorts. W. Salerno, X. Bai, E. Maxwell, P. Chang, O. Krasheninina, L. Habegger, A. Carroll, J.G. Reid.

285/9:00 SV genotyping in large population cohorts utilizing sequence graphs. S. Chen, E. Dolzhenko, A.M. Gross, B.R. Lajoie, P. Krusche, R. Petrovski, R.M. Sherman, F. Schlesinger, D.R. Bentley, M.C. Schatz, F.J. Sedlazeck, M.A. Eberle.

286/9:15 Leveraging a cell-line cohort as a clinical reference panel: Analysis of high coverage 1000 genomes sequencing data. A.M. Gross, B.R. Lajoie, D.R. Bentley, M.A. Eberle, R.J. Taft.


Saturday, October 19

8:30 AM–9:30 AM

Concurrent Platform Session G : Non-CME

94. New Approaches for Novel Insights into Genetic Associations in Large-scale EHR and Biobank Studies

Grand Ballroom B, Level 3, Convention Center

Moderators: Andrew Paterson, Hosp Sick Children, Toronto, Canada
  Qiongshi Lu, Univ Wisconsin Madison

 

287/8:30 Prescription medication data improves genetic discoveries in EHR-based studies. T. Kiiskinen, A.S. Havulinna, J. Karjalainen, M. Kurki, S. Lemmelä, N.J. Mars, V. Salomaa, H. Laivuori, M. Daly, A. Palotie, S. Ripatti, FinnGen.

288/8:45 Genome-wide survey of parent-of-origin effects on EHR-derived quantitative traits in 90k DiscovEHR cohort. H. Kim, J. Staples, A. Marcketta, B. Ye, C. Gao, A. Shuldiner, C. Van Hout, RGC-Geisinger DiscovEHR Collaboration.

289/9:00 UK Biobank participants that live more than 20 km from their birthplace have higher socioeconomic and health correlates. I. Woods, A. Williams.

290/9:15 Large-scale identity-by-descent mapping in a biobank with more than 95,000 individuals identifies novel genome-wide significant regions associated with serum lipid levels. H.-H. Chen, L.E. Petty, Q.S. Wells, J.E. Below.


Saturday, October 19

8:30 AM–9:30 AM

Concurrent Platform Session G : Non-CME

95. Large-scale Phenotype Association Studies

Grand Ballroom C, Level 3, Convention Center

Moderators: Myriam Fornage, Univ Texas Hlth Sci Cent Houston
  Erin Ramos, NHGRI, Bethesda

 

291/8:30 Phenome-wide association study of loss of function variants in 128,382 UK Biobank whole exome sequences. M.M. Parker, L.D. Ward, G. Hinkle, P. Nioi.

292/8:45 An eQTL analysis of RNA-seq data from 13,175 individuals using a personalized transcriptome. G.H. Halldorsson, B. Gunnarsson, R.L. Gudmundsson, B.V. Halldorsson, S.A. Gudjonsson, D.F. Gudbjartsson, P. Sulem, O.TH. Magnusson, U. Thorsteinsdottir, K. Stefansson, P. Melsted.

293/9:00 Phenome-wide association study using the EHR-linked BioVU biobank links GREM2 variant Q76E to high risk of anemia. A.K. Hatzopoulos, D.H. Wu, E. Farber-Eger, Q.S. Wells.

294/9:15 Using the history of biochemistry to illuminate the genetic architecture of metabolite GWAS and its implications for complex human phenotypes. E.B. Fauman, P. Surendran, I.D. Stewart, L.A. Lotta, K. Suhre, G. Kastenmuller, J. Danesh, N.J. Wareham, A. Butterworth, C. Langenberg.


Saturday, October 19

8:30 AM–9:30 AM

Concurrent Platform Session G : Non-CME

96. Computational Methods for Genetic Data

Room 310A, Level 3, Convention Center

Moderators: Alejandro Nato, Marshall Univ, Huntington
  Joan E. Bailey-Wilson, NHGRI, Bethesda

 

295/8:30 Universal LD blocks in the human genome. S. Christensen, J.N.J. McManus.

296/8:45 Public programmatic access to GWAS summary statistics and analytical methods. M. von Grotthuss, J. Massung, B. Alexander, L. Caulkins, M. Costanzo, M. Duby, C. Gilbert, D.K. Jang, R. Koesterer, P. Singh, O. Ruebenacker, A. Boughton, R. Welch, M. Boehnke, N. Burtt, J. Flannick.

297/9:00 The unbiased length spectrum of human de novo mutations in 4,330 children. A. Farrell, W. Richards, A. Docherty, H. Coon, G. Marth.

298/9:15 Estimating assortative mating and its changes over time in samples of unrelated individuals. P. Turley, R. Li, L. Yengo, D. Cesarini, D. Benjamin, B. Neale, P. Visscher, M. Kimball.


Saturday, October 19

8:30 AM–9:30 AM

Concurrent Platform Session G : Non-CME

97. Chromosomes to Cell-free DNA: Balancing Genetic Contributions

Room 360D, Level 3, Convention Center

Moderators: David Buchner, Case Western Reserve Univ, Cleveland
  Bing Yao, Emory Univ, Atlanta

 

299/8:30 X-chromosome dosage compensation dynamics in human early embryos. G. Fan, K. Huang, Q. Zeng, Y. Feng, Y. Hu, L. Qin, Q. An, B. Lv, J. Liu, Z. Xue.

300/8:45 Detection of uniparental disomy in a population of 32,000 clinical exome trios. J. Scuffins, J. Keller-Ramey, L. Havens, G. Douglas, N. Robin, N. Rudy, K. Retterer.

301/9:00 Comprehensive estimation of the tissue of origin of circulating cell-free DNA. C. Caggiano, B. Celona, F. Garton, B. Black, N. Wray, A. Dahl, N. Zaitlen.

302/9:15 Non-invasive monitoring of kidney transplant conditions via donor-derived cell-free DNA. P. Nguyen, H. Nakaoka, K. Saigo, T. Hayano, I. Inoue.


Saturday, October 19

8:30 AM–9:30 AM

Concurrent Platform Session G : Non-CME

98. Gene Regulation and Neurological Phenotypes

Room 361D, Level 3, Convention Center

Moderators: Molly Gasperini, Univ Washington, Seattle
  Jacob Loupe, HudsonAlpha Institute Biotechnology, Huntsville

 

303/8:30 Massively parallel characterization of regulatory dynamics during neural induction. A. Kreimer, F. Inoue, T. Ashuach, N. Ahituv, N. Yosef.

304/8:45 The ATP-dependent chromatin remodeler CHD7 is critical for neuronal lineage differentiation by changing chromatin accessibility and nascent RNA. D.F. Hannum, H. Yao, S.F. Hill, R.D. Albanus, W. Lou, J.M. Skidmore, G.J. Sanchez, A. Saiakhova, S.L. Bielas, P.C. Scacheri, M. Ljungman, S.C.J. Parker, D.M. Martin.

305/9:00 Identifying critical downstream gene targets of transcription factors associated with disease. A.M. Barbeau, A. Hoang, K. Hazel, O. Corradin.

306/9:15 Spatially-resolved single-cell chromatin accessibility in the adult mouse brain. C.A. Thornton, A. Mishra, A.P. Barnes, B.J. O'Roak, A.C. Adey.


Saturday, October 19

8:30 AM–9:30 AM

Concurrent Platform Session G : Non-CME

99. Precision Medicine: Rare Variants

Room 370A, Level 3, Convention Center

Moderators: Hilary Vernon, Johns Hopkins Univ Sch Med, Baltimore
  Irini Manoli, NIH/NHGRI, Bethesda

 

307/8:30 AT-007, a novel CNS penetrant aldose reductase inhibitor prevents the metabolic and tissue specific abnormalities of Galactosemia, in a GALT deficient rat model of disease. R. Perfetti, S. Shendelman.

308/8:45 Taurine supplementation treatment for progressive retinal degeneration and cardiomyopathy caused by a novel recessive gene SLC6A6. M. Ansar, E. Ranza, M. Shetty, S.A. Paracha, M. Azam, M.T. Sarwar, I. Kern, O. Farooq, C.J. Pournaras, A. Malcles, L. Ali, F.A. Santoni, P. Makrythanasis, R. Qamar, J. Ahmed, K. Henry, S.E. Antonarakis.

309/9:00 A de novo CLCN7 variant alters lysosomal pH and leads to lysosomal storage and albinism. M.C. Malicdan, E.R. Nicoli, M. Weston, M. Hackbarth, A. Becerril, A. Larson, W.M. Zein, P.R. Baker II, J.D. Burke, H. Dorward, M. Davids, Y. Huang, D.R. Adams, P.M. Zerfas, D. Chen, T.C. Markello, C. Toro, T. Wood, G. Elliott, M. Vu, U.D.N. Undiagnosed Diseases Network, W. Zheng, L. Garrett, C.J. Tifft, W.A. Gahl, D.L. Day-Salvatore, J.A. Mindell.

310/9:15 Results of an open-label phase 2 study of ManNAc in subjects with GNE myopathy. N. Carrillo, M.C. Malicdan, K. Bradley, C. Slota, J.A. Shrader, P. Leoyklang, B. Class, J. Perreault, C. Ciccone, R. Parks, M. Quintana, J. Galen, J. Heiss, S. Van Wart, C.T. Driscoll, S.M. Berry, M. Huizing, W.A. W.A.


Saturday, October 19

8:30 AM–9:30 AM

Concurrent Platform Session G : Non-CME

100. Uncovering Genome Complexity and Function with Long-read Sequencing

Room 371A, Level 3, Convention Center

Moderators: Chad Shaw, Baylor Col Med, Houston
  Glennis Logsdon, Univ Washington, Seattle

 

311/8:30 Long-read transcriptome sequencing in over 60 human tissue samples reveals isoform diversity. B. Cummings, G. Garborcauskas, M. Micorescu, T. Bowers, M.T. Costello, F. Aguet, K. Ardlie, D.G. MacArthur.

312/8:45 Refining polymorphic retrotransposon insertions in human genomes. W. Zhou, R. Mills.

313/9:00 Incorporating long transcriptomic data into GENCODE. J.E. Loveland, J.M. Mudge, J.M. Gonzalez, T.J. Hunt, A. Frankish, P. Flicek, GENCODE Consortium.

314/9:15 What comes next? Long-read whole genome sequencing (WGS) to solve non-diagnostic whole exome sequencing and short-read WGS. N. Sobreira, S. Aganezov, R. Sherman, E. Wholer, E. Martin, C. Bradburne, S. Raskin, D. Valle, M. Schatz.


Saturday, October 19

9:45 AM–11:15 AM

Concurrent Platform Session H

101. Pharmacogenomics and Gene Therapy

Hall B, Level 1, Convention Center

Moderators: Kathleen Fisch, UC San Diego Hlth
  Steven Scherer, Baylor Col Med, Houston

 

315/9:45 Impact of pharmacogenetic testing on statin outcomes: Primary results from the Integrating Pharmacogenetics in Clinical Care (I-PICC) Study randomized trial. C.A. Brunette, S. Advani, A. Hage, S.-J. Seo, S.J. Miller, N. Majahalme, A.J. Zimolzak, J.L. Vassy.

316/10:00 Pharmacy-supported return of over 10,000 pharmacogenomics test results: Semi-urgent eConsult data from the Mayo-Baylor RIGHT10K Pharmacogenomics Consortium Study. J. Wright, E. Matey, J. Giri, R. El Melik, L. Oyen, J. Anderson, W. Nicholson.

317/10:15 Genome-wide association study of alanine transaminase and aspartate transaminase identifies novel variants with divergent effects on metabolic traits. V.L. Chen, X. Du, Y. Chen, S.K. Handelman, E.K. Speliotes.

318/10:30 Massively parallel functional profiling of CYP2C9 variants using a yeast activity assay. C.J. Amorosi, L.H. Wong, K.A. Sitko, M.G. McDonald, A.E. Rettie, D.M. Fowler, M.J. Dunham.

319/10:45 Targeted in-frame deletion of the F8 B domain to restore FVIII function in patient-iPSCs derived ECs. D. Liang, Z. Hu, M. Zhou, L. Wu.

320/11:00 A viable mouse model of cblC deficiency displays growth failure and reduced survival which are rescued by hydroxocobalamin and AAV gene therapy. J.L. Sloan, K.C. Murphy, M. Arnold, N.P. Achilly, G. Elliot, P. Zerfas, V. Hoffmann, B.P. Brooks, D. Watkins, D.S. Rosenblatt, C.P. Venditti.


Saturday, October 19

9:45 AM–11:15 AM

Concurrent Platform Session H

102. Darwin's Tumor: Mutation, Selection, and Evolution in Cancer Genomes

Grand Ballroom A, Level 3, Convention Center

Moderators: David Wheeler, Baylor Col Med, Houston
  Athea Vichas, Fred Hutchinson Cancer Res Cent, Seattle

 

321/9:45 The evolutionary history of 2,658 cancers. P. Van Loo, C. Jolly, I. Leshchiner, S.C. Dentro, S. Gonzalez, P.T. Spellman, D.C. Wedge, M. Gerstung, the PCAWG Evolution and Heterogeneity Working Group and the PCAWG network.

322/10:00 Unexpectedly high rates of recurrent somatic mutations in cancer genomes reveal mutational processes, the structure and behavior of the genome to stress and allow clinically relevant classification. I.G. Gut, M.D. Stobbe, G.A. Thun, J.P. Whalley, M. Oliva, E. Raineri.

323/10:15 Integrated analysis of NGS and optical mapping resolves the complex structure of highly rearranged focal amplifications in cancer. J. Luebeck, V. Deshpande, C. Coruh, S. Raisi, D. Pai, S. Wu, C.S. Zhang, K.M. Turner, J.A. Law, P.S. Mischel, V. Bafna.

324/10:30 Detailed modeling of positive selection significantly improves detection of cancer driver genes. S. Zhao, X. He, M. Stephens.

325/10:45 Detecting cancer vulnerabilities through gene networks under purifying selection. H. Horn, A. Gupta, C. Fagre, P. Razaz, A. Kim, M. Lawrence, G. Getz, J.T. Neal, K. Lage.

326/11:00 Inferring clonal lineages and mutational chronologies in triple negative breast cancer using high-throughput single cell DNA sequencing. J. Leighton, M. Hu, A. Davis, E. Sei, Y. Wong, N. Navin.


Saturday, October 19

9:45 AM–11:15 AM

Concurrent Platform Session H

103. DNA Methylation

Grand Ballroom B, Level 3, Convention Center

Moderators: Andrew Sharp, Icahn Sch Med Mount Sinai, New York
  Shaunna Clark, Michigan State Univ, East Lansing

 

327/9:45 Extreme methylation variation from whole-genome bisulphite sequencing among patients with negative clinical exomes. T. Pastinen, W. Cheung, N. Miller, S. Herd, J. Johnston, I. Thiffault, E. Farrow, A. Walter, M. Gibson, S. Younger, C. Berrios, E. Grundberg, D. Zhou, C. Lawson, L. Grote, S. Hughes, C. Schwager, E. Fleming, K. Engleman, L. Cross, J. Kussman, H. Welsh, J. Jenkins, R. Gadea, M. Strenk, J. Gannon, S. Amudhavali, E. Rush, B. Heese, C. Saunders.

328/10:00 Clonal hematopoiesis of indeterminate potential and epigenetic age acceleration. D. Nachun, A. Lu, A. Bick, P. Natarajan, D. Levy, A. Reiner, J. Wilson, S. Horvath, S. Jaiswal, NHLBI Trans-Omics for Precision Medicine.

329/10:15 Exploiting omics to measure genome-by-environment interactions. C. Amador, Y. Zeng, R. Walker, A. McIntosh, K. Evans, D. Porteous, A. Campbell, C. Hayward, P. Navarro, C. Haley.

330/10:30 Cell-type specific DNA methylation QTL of primary melanocytes with multi-QTL integration enhances melanoma GWAS annotation beyond eQTL. J. Choi, T. Zhang, M. Kovacs, M. Xu, A. Vu, S. Loftus, W. Pavan, D.T. Bishop, A.J. Stratigos, P. Ghiorzo, K. Peris, G.J. Mann, G.L. Radford-Smith, N.G. Martin, S.V. Ward, S. Puig, D.L. Duffy, F. Demenais, E. Nagore, D.C. Whiteman, S. MacGregor, M.T. Landi, M.H. Law, M.M. Iles, J. Shi, B. Pasaniuc, K.M. Brown, Melanoma Meta-Analysis Consortium.

331/10:45 Estimation of total mediation effect for multiple types of high-dimensional omics mediators in over 3500 individuals provides novel insight into aging-related variation in blood pressure. Y. Zhao, T. Yang, J. Zou, Z. Wang, J. Niu, H. Chen, P. Wei.

332/11:00 TET3 deficiency: Delineation of the first human Mendelian disorder of the DNA demethylation machinery. J.A. Fahrner, A. Petracovici, C. He, H.W. Moore, R. Louie, M. Ansar, R.L.P. Santos-Cortez, E.J. Prijoles, R. Bend, B. Keren, C. Mignot, M.C. Nougues, K. Õunap, T. Reimand, S. Pajusalu, J. Buratti, E.G. Seaby, K. McWalter, A. Telegrafi, T. Cottrell, S. Sithambaram, S. Douzgou, D. Baldridge, M. Shinawi, S.M. Leal, G.B. Schaefer, R. Stevenson, S. Banka, R. Bonasio, D.B. Beck, Deciphering Developmental Disorders study.


Saturday, October 19

9:45 AM–11:15 AM

Concurrent Platform Session H

104. Enhanced Analysis and Correction of Single-cell Data

Grand Ballroom C, Level 3, Convention Center

Moderators: Anne-Christian Hauschild, Phillips-Universität Marburg, Germany
  Yun Li, Univ North Carolina Chapel Hill

 

333/9:45 Transfer learning significantly improved clustering accuracy in single-cell RNA-seq analysis. J. Hu, X. Li, G. Hu, M. Li.

334/10:00 SMNN: Batch effect correction for single-cell RNA-seq data via supervised mutual nearest neighbor detection. Y. Yang, G. Li, H. Qian, Y. Li.

335/10:15 A machine learning approach to enhance resolution of single-nucleus RNA-seq data by removing debris contamination. M. Alvarez, E. Rahmani, B. Jew, K.M. Garske, Z. Miao, J.N. Benhammou, C.J. Ye, J.R. Pisegna, K.H. Pietiläinen, E. Halperin, P. Pajukanta.

336/10:30 Cell-ID enables the identification of rare individual cells and their reproducible gene signatures across independent single-cell RNA-seq datasets. A. Rausell, A. Cortal.

337/10:45 Model selection-based scRNA-seq quantitation algorithm that controls overfitting and unwarranted imputation of technical zeros. K. Choi, D.A. Skelly, M.J. Vincent, G.A. Churchill.

338/11:00 Accurate estimation of cell composition in bulk expression through robust integration of single-cell information. B. Jew, M. Alvarez, E. Rahmani, Z. Miao, A. Ko, J.H. Sul, K.H. Pietiläinen, P. Pajukanta, E. Halperin.


Saturday, October 19

9:45 AM–11:15 AM

Concurrent Platform Session H

105. Mechanisms of Immune Cell Phenotypes and Clonal Hematopoiesis

Room 310A, Level 3, Convention Center

Moderators: Suna Onengut-Gumuscu, Univ Virginia, Charlottesville
  Vijai Joseph, Memorial Sloan Kettering Cancer Cent, New York

 

339/9:45 The genetic architecture of hematological traits within and between populations. G. Lettre, M.H. Chen, L. Raffield, A. Mousas, T. Jiang, P. Akbari, S. Sakaue, E.L. Bao, C.A. Lareau, M. Chen, C.W.K. Chiang, Y. Okada, V.G. Sankaran, N. Soranzo, A. Reiner, A.D. Johnson, P.L. Auer, on behalf of the Blood-Cell Consortium.

340/10:00 Large scale GWAS identifies clinically relevant rare variation for blood cell traits. L.M. Raffield, D. Vuckovic, E.L. Bao, C.A. Lareau, P. Akbari, M. Chen, T. Jiang, A. Mousas, A. Reiner, W.J. Astle, A.S. Butterworth, A.D. Johnson, P. Auer, G. Lettre, V.G. Sankaran, N. Soranzo, Blood Cell Traits Consortium (BCX).

341/10:15 Age, sex, and genetics influence the abundance of infiltrating immune cells in human tissues. A.R. Marderstein, M. Uppal, A. Verma, B. Bhinder, J. Mezey, A.G. Clark, O. Elemento.

342/10:30 Multimodal single-cell analysis of 70,000 human memory T cells characterizes genetic associations with immune cell states and gene expression in a Peruvian tuberculosis progression cohort. A. Nathan, J.I. Beynor, S. Suliman, Y. Baglaenko, K. Ishigaki, Y. Luo, I. Van Rhijn, M.B. Murray, D.B. Moody, S. Raychaudhuri.

343/10:45 Monogenic and polygenic inheritance become instruments for clonal selection. P. Loh, G. Genovese, S.A. McCarroll.

344/11:00 Inherited causes and clinical consequences of clonal hematopoiesis from 100,002 whole genomes. J. Weinstock, A. Bick, S. Nandakumar, V. Sankaran, A. Reiner, S. Jaiswal, G. Abecasis, P. Natarajan, S. Kathiresan, on behalf of the NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium.


Saturday, October 19

9:45 AM–11:15 AM

Concurrent Platform Session H

106. New Insights into Rare Skeletal, Growth, and Vascular Disorders

Room 360D, Level 3, Convention Center

Moderators: Beth Kozel, NIH/NHLBI, Bethesda
  Brian Chung, Univ Hong Kong, China

 

349/9:45 Mutations in ANAPC1, encoding a scaffold subunit of the anaphase promoting complex, cause Rothmund-Thomson syndrome type 1. P. Campeau, N.F. Ajeawung, T.T.M. Nguyen, L. Lu, T.J. Kucharski, J. Rousseau, S. Molidperee, J. Atienza, I. Gamache, W. Jin, S.E. Plon, B.H. Lee, J.G. Teodoro, L.L. Wang.

346/10:00 Understanding the physiological role of DDRGK1 from Shohat-type SEMD: Novel regulatory mechanism of matrix proteins. Y. Bae, M. Weisz-Hubshman, A. Egunsola, M. Jiang, Z. Yu, Y. Chen, B. Lee.

347/10:15 The Maenli long non-coding RNA locus controls En1 expression and limb development. A. Superti-Furga, L. Allou, S. Balzano, A. Magg, M. Quinodoz, B. Royer-Bertrand, R. Schöpflin, W.L. Chan, E. Speck-Martins, D. Rocha de Carvalho, L. Farage, C. Marques Lourenço, S. Rajagopal, S. Nampoothiri, B. Campos-Xavier, C. Chiesa, F. Niel-Bütschi, L. Wittler, B. Timmermann, S. Unger, C. Rivolta, P. Grote, S. Mundlos.

345/10:30 Heterozygous deleterious variants in WBP11 cause multiple congenital anomalies in humans and mice. G. Chapman, E.M.M.A. Martin, A. Enriquez, D.B. Sparrow, D.T. Humphreys, K.R. Iyer, J.A. Greasby, P. Leo, E.L. Duncan, C. Dimartino, J. Amiel, N.L.M. Sobreira, D. Lehalle, H.M. Rasouly, A.G. Gharavi, R.D. Steiner, C. Raggio, R. Blank, C.T. Gordon, R. Jobling, P. Giampietro, S.L. Dunwoodie.

348/10:45 Variants in the HIF-1 pathway are associated with Ollier disease and Maffucci syndrome. S. Robbins, R. Martin, B. Cohen, C. Haldeman-Englert, M. Cernach, G. Gottesman, G. Semenza, D. Valle, N. Sobreira.

350/11:00 Mutations in ephrinB2-EphB4-RASA1 signaling underlie Vein of Galen Malformation. X. Zeng, A. Hunt, S.C. Jin, S. Conine, A. Allocco, D. Duran, C. Nelson-Williams, M. Sorscher, E. Loring, J. Klein, M. DiLuna, C. Matouk, S. Alper, M. Komiyama, A. Ducruet, J. Zabramski, A. Dardik, B. Walcott, C. Stapleton, B. Aagaard-Kienitz, G. Rodesch, E. Jackson, E. Smith, D. Orbach, A. Berenstein, K. Bilguvar, M. Vikkula, M. Gunel, R.P. Lifton, K.T. Kahle.


Saturday, October 19

9:45 AM–11:15 AM

Concurrent Platform Session H

107. Methods and Resources for Improved Genomic Variant Interpretation

Room 361D, Level 3, Convention Center

Moderators: Jennifer E. Posey, Baylor Col Med, Houston
  Christian Marshall, Hosp Sick Children, Toronto, Canada

 

351/9:45 gnomAD-SV: An open resource of structural variation for medical and population genetics. R.L. Collins, H. Brand, K.J. Karczewski, X. Zhao, J. Alföldi, A.V. Khera, L.C. Francioli, L.D. Gauthier, H. Wang, N.A. Watts, M. Solomonson, A. O’Donnell-Luria, A. Baumann, R. Munshi, C. Lowther, M. Walker, C. Whelan, E. Valkanas, J. Fu, A. Philippakis, E. Lander, S. Gabriel, B.M. Neale, S. Kathiresan, M.J. Daly, E. Banks, D.G. MacArthur, M.E. Talkowski, The Genome Aggregation (gnomAD) Consortium.

352/10:00 Recommendations for determining the clinical validity of functional studies for use in variant interpretation. S. Brnich, A. Abou Tayoun, M.S. Greenblatt, C.D. Heinen, D. Kanavy, X. Luo, S.M. McNulty, L.M. Starita, S.V. Tavtigian, S.M. Harrison, L.G. Biesecker, J.S. Berg, ClinGen Sequence Variant Interpretation Working Group.

353/10:15 Validation of scoring metrics to guide the classification of constitutional copy number variants. E. Riggs, E. Andersen, A. Cherry, S. Kantarci, H. Kearney, A. Patel, G. Raca, D. Ritter, S. South, E. Thorland, D. Pineda-Alvarez, S. Aradhya, C. Martin.

354/10:30 StrVCTURE: A supervised learning method to predict the pathogenicity of structural variants. A.G. Sharo, S.E. Brenner.

355/10:45 A digital diagnosis: The use of artificial intelligence in clinical exome analysis. A.B. Potter, T.D. O'Brien, N.E. Campbell, A. Frankenstein, A. Kulkarni, J.H. Letaw, C.S. Richards.

356/11:00 Breaking the interpretation bottleneck: Examining the utility of an automated genomic interpretation algorithm in a clinical genetic lab. L. Meng, R. Attali, R. Dominguez-Vidana, C. Taborda, K. Bui, Y. Regev, N. Mizrahi, A. Lev-Libfeld, T. Talmy, P. Smirin-Yosef, R. Xiao, I. Machol, C. Eng, F. Xia, S. Tzur.


Saturday, October 19

9:45 AM–11:15 AM

Concurrent Platform Session H

108. Prenatal Diagnosis and Pregnancy Loss

Room 370A, Level 3, Convention Center

Moderators: William Wilson, Univ Virginia Hlth Sys, Charlottesville
  Elizabeth Goehring, Emory Univ, Atlanta

 

357/9:45 Low-pass whole-genome sequencing versus chromosomal microarray analysis: Prospective implementation in prenatal diagnosis. Z. Dong, H. Wang, M. Chau, T.Y. Leung, S.W. Cheung, Y.K. Kwok, C.C. Morton, Y. Zhu, K.W. Choy.

358/10:00 Low-pass WGS as an alternate cost-effective solution to chromosomal microarray analysis. J. Shen, T. Chiang, W. He, M. Wang, Y. Yang, X. Wang.

359/10:15 Yield overpowers risk in amniocentesis performed in low-risk pregnancies. M. Shohat, K. Hod, B. Azaria, I. Abadi-Korek, Y. Segal, R. Berger, R. Moshonov.

360/10:30 The role of compound heterozygotes and de novo mutations in early human pregnancy loss. S.K. Garushyants, E. Nabieva, M.D. Logacheva, T.V. Neretina, A. Fedotova, V. Moskalenko, N. Libman, R. Bikanov, E. Pomerantseva, D. Pyankov, I. Kanivets, T. Serebrennikova, E. Glazyrina, G.A. Bazykin.

361/10:45 Exome sequencing of 268 stillbirth cases emphasizes the importance of diagnostic sequencing and implicates highly constrained novel genes not currently associated with human disease. J.L. Giordano, K. Stanley, C. Buchovecky, A. Thomas, M. Ganapathi, J. Liao, A.V. Dharmadhikari, A. Revah Politi, M. Ernst, N. Lippa, H. Holmes, R.M. Silver, N. Stong, V. Aggarwal, R. Wapner, D. Goldstein, Stillbirth Collaborative Research Network.

362/11:00 Exome sequencing for infants with a prenatally identified fetal structural anomaly: Diagnostic yield and changes in management. A.S. Freed, S.V. Clowes Candadai, M.C. Sikes, J. Thies, H.M. Byers, J.N. Dines, M.K. Ndugga-Kabuye, K. Fogus, H.C. Mefford, C. Lam, M.P. Adam, A. Sun, R. DiGeronimo, K.M. Dipple, G.H. Deutsch, Z.C. Billimoria, J.T. Bennett.


Saturday, October 19

9:45 AM–11:15 AM

Concurrent Platform Session H

109. Novel Methods in Variant Association Studies

Room 371A, Level 3, Convention Center

Moderators: Florence Demenais, INSERM, Paris, France
  Maisa Pinheiro, NCI, Rockville

 

363/9:45 MRP: Exome rare-variant analysis via Bayesian model comparison prioritizes strong risk and protective effects across biomarkers and diseases. G.R. Venkataraman, M. Aguirre, Y. Tanigawa, M.A. Rivas.

364/10:00 Correlations between polygenic risk score predictors suggest a method to detect sub-phenotypes in GWAS cohorts. J. Yuan, H. Xing, A. Lamy, I. Pe'er.

365/10:15 Using model predictions as quantitative traits improves power in a genome-wide association study of acute ischemic stroke in the UK Biobank. P.M. Thangaraj, N.P. Tatonetti.

366/10:30 Detection of local genetic correlation by a scan statistic approach. H. Guo, Q. Lu, L. Hou.

367/10:45 Mitigating batch effects in >23,000 WGS samples for a case-control GWAS of kidney disease. T. Soare, W. Zhang, A. Tebbe, V. Mandal, D. Borges-Rivera, N. Chennagiri, M. Kretzler, G. Nadkarni, R. Gbadegesin, J. Wenke, D. MacArthur, J. Reilly, P. Mundel, L. Walsh, T. Tibbitts.

368/11:00 Identifying robust trans-associations via a cross-condition mediation analysis and validating the trait-associations for trans-genes of GWAS loci. L.S. Chen, F. Yang, K.J. Gleason, J. Wang, J. Duan, X. He, B.L. Pierce.


Saturday, October 19

11:30 AM–12:30 PM

110. Featured Plenary Abstract Session IV

Hall B, Level 1, Convention Center

Moderators: Laura K. Conlin, ASHG 2019 Program Committee
  Mete Civelek, ASHG 2019 Program Committee

 

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

 

369/11:30 Phase 2/3 trial to assess the safety and efficacy of Lenti-D autologous hematopoietic stem cell gene therapy for cerebral adrenoleukodystrophy. F. Eichler, C. Duncan, P. Orchard, S. De Oliveira, A. Thrasher, T. Lund, C. Sevin, P. Gissen, H. Amartino, N. Smith, E. Shamir, W. Chin, E. McNeil, P. Aubourg, D. Williams.

370/11:50 The first human single cell atlas of the Substantia nigra reveals novel cell-specific pathways associated with the genetic risk of Parkinson’s disease and neuropsychiatric disorders. C. Sandor, D. Agarwal, V. Volpato, T. Caffrey, J. Alegre-Abarrategui, R. Wade-Martins, C. Webber.

371/12:10 Genomic analyses in 3 million individuals identify genetic determinants of questionnaire response bias and study participation with potential implications for GWAS interpretation. A. Ganna, G. Mignogna, B. Hollis, C. Carey, R. Walters, M.D. Van der Zee, . 23andMe Research Team, P. Joshi, N. Pirastu, B. Neale, M. Nivard, J.R.B. Perry.


Saturday, October 19

1:00 PM–2:00 PM

111. Closing Symposium: What's on the Horizon?

Hall B, Level 1, Convention Center

Moderator: Kiran Musunuru, ASHG 2019 Program Chair

 

Stay through Saturday for the final session of the meeting to catch up on the most exciting discoveries presented during the week. Leave Houston prepared to tell your colleagues what they missed. Scientific leaders from the ASHG Program Committee and key speakers will share important breakthroughs and practical takeaways in this energetic, interactive session rounding out the meeting.