Page 82 - ASHG 2012 Annual Meeting Program Guide

INVITED AND PLATFORM SESSIONS
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Wednesday, November 7
8:00
AM
–10:00
AM
Concurrent Invited Session I (3-10)
SESSION 7 – Age-Related Macular Degeneration–
GWAS and Beyond: Guiding Light for the Complex
Neurodegenerative Diseases
Gateway Ballroom 104, Lower Level South, Moscone
Center
Moderators
:
Anand Swaroop, NEI/NIH; Hemin Chin,
NEI/NIH
AMD is a complex multi-factorial neurodegenerative
disease that is a major cause of visual impairment in
the elderly. Genetic linkage and genome-wide
association studies (GWAS) have been immensely
successful in identifying genetic susceptibility loci in
AMD and in providing insights into cellular pathways
underlying pathogenesis of the disease. Numerous
groups worldwide have validated the strong
association of variants at CFH and ARMS2/HTRA1 loci
with AMD risk, and genome-wide association studies
have suggested the involvement of complement,
extracellular matrix, angiogenesis and HDL cholesterol
pathways. This session will discuss the current
progress to carry out comprehensive genetic analyses
of AMD, highlighting experimental approaches that
may be applicable to other complex traits and
multigenic diseases. The speakers in this session will
provide the current status of meta-analysis of AMD-
GWAS, targeted resequencing, and whole exome
sequencing efforts to discover or search for rare
causal variants and functional pathways, and
diagnostic/therapeutic implications of genetic variants.
Additionally, we will discuss the relevance of AMD
genetics for other complex neurodegenerative
diseases and the future of genetic studies.
8:00
AM
The bigger the better: Searching for
novel loci for age-related macular degeneration in
a large consortium effort.
I. Heid. Regensburg Univ.
Med. Ctr., Germany.
8:30
AM
From genetic association to causal
alleles by resequencing and exome arrays: The
stage after GWAS.
G. Abecasis. Univ. of Michigan.
9:00
AM
An integrated hypothesis of the
development and progression of age-related
macular degeneration based upon available genetic
and biological data.
G. S. Hageman. Univ. of Utah.
9:30
AM
An updated recipe for Mendel’s pea
soup.
M. A. Pericak-Vance. Univ. of Miami Miller Sch.
of Med.
Wednesday, November 7
8:00
AM
–10:00
AM
Concurrent Invited Session I (3-10)
SESSION 8 – “Yes Virginia, Family Studies Really Are
Useful for Complex Traits in the Next-Generation
Sequencing Era” (session in honor of Dr. Robert
Elston’s contributions to human genetics in the year
of his 80th birthday)
Room 124, Lower Level North, Moscone Center
Moderators
:
Michael A. Province, Washington Univ. in
St. Louis; Francoise Clerget-Darpoux, INSERM U781,
Univ. Paris V, France.
The pros and cons of family designs as NGS targets in
dissecting complex traits are presented. In the linkage
era, family studies were ubiquitous, but they were
largely neglected in the GWAS era, which
concentrated mostly on unrelated subjects. But as
attention now moves from the common to the rare
variants that can only be completely interrogated
through sequencing, it is useful to at least consider
whether the designs that were optimal for GWAS
remain so for NGS studies. Pedigrees seem to have at
least some advantages over studies of unrelateds for
studying rare variation. First, it may be easier to
distinguish true rare variant calls from sequence errors
in family designs than it is in unrelated cohorts, since
there is the added dimension of pedigree consistency
information, especially for low coverage. Second, a
key statistical challenge to analyzing the phenotype/
genotype correlation with rare variants, is finding
enough copies of any one variant allele with which to
make inferences (hence the various collapsing or
burden tests, which combine multiple nearby rare
variants into a single test). For any given very rare
allele, sampling additional unrelateds is an inefficient
strategy to find more copies of that allele, whereas
family members of allele carriers are much more likely
to be allele carriers themselves. On the other hand, a
disadvantage of family designs is that there is a
smaller diversity of founder mutations, so less of the
overall population of alleles is measured per individual.
This session emphasizes the results of real sequencing
studies in pedigrees as well as simulation results to
delineate the areas in which family designs offer
advantages and where they offer disadvantages over
sequencing unrelated subjects, such as case-control
designs.
8:00
AM
Whole genome sequencing in large
pedigrees for the identification of human QTLs.
J.
Blangero. Texas Biomed. Res. Inst., Austin.
8:30
AM
Linkage and association information
should be considered as complementary and not
redundant.
F. Clerget-Darpoux. INSERM U781, Univ.
Paris V, France.
9:00
AM
Power to find rare causal variants in
pedigrees.
M. A. Province. Washington Univ. in St.
Louis.
9:30
AM
Whither human genetics?
R. C. Elston.
Case Western Reserve Univ.
INVITED AND PLATFORM SESSIONS
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