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MathBio Seminar

Monday, April 4, 2016 - 4:00pm

Guy Sella

Columbia University


University of Pennsylvania

318 Carolyn Lynch Lab

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.