Oct. 24-26, 2009, Yingjie Overseas Exchange Center, Peking University, Beijing, China中文版

The Genetic Architecture of a Complex Trait: What evolutionary biology can tell us about genome-wide association studies

Adam Eyre-Walker

University of Sussex, UK

Abstract

Over the last two or three years several hundred mutations have been discovered by genome-wide association studies. However, with few exceptions, these explain little of the variance in the disease or trait they are associated with. The reason for this lack of explanatory power has been the subject of much speculation. Here I explore one of these explanations - that mutations which affect traits also affect fitness, either because the trait is a component of fitness, or because the mutations have pleiotropic effects on fitness. I show, under quite general conditions, that if the average strength of selection acting on the mutations, which affect a trait, are even quite weakly selected, then the vast majority of the variance in the trait is expected to be contributed by mutations at low frequency in the population. Such mutations will be difficult to detect using genome-wide association studies. Furthermore, I show that the total variance contributed by a category of mutations, say regulatory or protein coding mutations, is likely to be related to the mean strength of selection. It should therefore be possible to infer whether regulatory or protein coding changes contribute most to the variance in traits.

Adam Eyre-Walker

University of Sussex, UK

Biography

Adam Eyre-Walker was educated at Shrewsbury School, where Darwin was a student, Nottingham University and Edinburgh University, where he did his PhD with William G. Hill. He then did two post-doctoral research fellowships at Rutgers University, with Michael Bulmer and Brandom Gaut, before returning to the UK as a Royal Society University Research Fellow at the University of Sussex. He held his fellowship until 2004 when he became a Reader, before being promoted to Professor in 2005.