Lecturer: Prof. Guy Sella
Affiliation: Department of Biological Sciences
Columbia University
Abstract:
Many phenotypes of interest,
including susceptibility to many
common diseases, are “quantitative”,
meaning that the heritable variation
in the trait is largely due to numerous
genetic variants of small effects
segregating in the population. The
causes of quantitative genetic
variation have been studied in
evolutionary biology for over a
century. This pursuit has recently
come to the forefront of research in
human genetics as well, with the
push to map variants that underlie
heritable genetic variation in
phenotypes. Notably, since 2007,
genome-wide association studies
(GWAS) in humans have led to the
identification of thousands of
variants reproducibly associated
with hundreds of quantitative traits,
including susceptibility to a wide
variety of diseases. These studies
reveal intriguing differences among
traits in their genetic architecture
(i.e., the number of associated
variants, their effect sizes and
frequencies) and in the fraction of the
heritable variation explained.
Interpreting these findings has been
difficult, however, in no small part
because we lack generative models
relating population genetic processes
(e.g., pleiotropy, selection and genetic
drift) to the genetic architecture of
quantitative traits. I will present such
a model and discuss how it helps to
understand the results of GWAS. I
will also describe our preliminary
results using GWAS findings to learn
about the forces underlying heritable
variation in human height.