UGI Seminar - Prof Jonathan Pritchard, Stanford University

Professor Jonathan Pritchard
'How selection, pleiotropy and chance shape what we discover in genome-wide association studies'
Wednesday, 17 April at 1500hrs
AV Hill Lecture Theatre, Medical Sciences Building

Abstract:
Genome-wide association studies (GWAS) are an essential tool for studying how genetic variation impacts phenotypes. However, GWAS results are often hard to interpret, and may not highlight genes that we know are biologically important. This suggests a key question: What determines which variants or genes are discovered in GWAS? Using a mixture of theory and data analysis, we show that association studies prioritize variants that are most specific to the trait under study --- and not the variants and genes with the largest effects. This prioritization of specificity arises because natural selection acts on multiple axes of phenotypic variation and variants with less pleiotropy experience weaker selection. We use this insight to compare the types of genes discovered by GWAS and rare variant burden tests, and close with a discussion of how these insights can be used to interpret future studies.