Speakers

Dr. Jason Stajich, UC Riverside

 

Dr.Nancy Cox,University of Chicago

Abstract:

New Ways of Investigating the Genetic Architecture of Common Human Diseases and Complex Traits

Genome-wide association studies (GWAS) gave us unprecendented numbers of new discoveries of risk loci for common diseases and complex human traits. As has been publicly lamented, the relatively modest numbers of loci discovered for any particular phenotype, coupled with the small effect sizes of the most highly significant and reproducible associations insured that only a small proportion of the heritability previously estimated for these phenotypes was accounted for by the associated loci. Worse, these discoveries generated less insight into the underlying biology of common disease than we had expected, largely because the vast majority of associations are to genetic variants that are outside coding sequence; thus, for many of the associations, we do not know with certainty what gene(s) are implicated by an association. Recent advances in technology are permitting large numbers of samples from a variety of common diseases to be sequenced at least for all exonic variation, and in addition, new approaches have been developed that permit estimating heritability from large-scale genome data in aggregate. The combination of these two new ways of interrogating genomes are providing some additional illumination on the genetic architecture of common diseases and complex traits. We have begun to incorporate information on functional variation into these studies in ways that both highlight the contribution of classes of functional variation to overall heritability, and promise the ability to do genuine risk prediction. While the ability to do risk prediction offers many new research opportunities – and we will illustrate a number – it raises new challenges as well. In particular, ethical issues that geneticists had been able to avoid because we couldn’t really do good risk prediction for common disease can no longer be avoided.