Genome-wide significance for dense SNP and resequencing data

Abstract

The problem of multiple testing is an important aspect of genome-wide association studies, and will become more important as marker densities increase. The problem has been tackled with permutation and false discovery rate procedures and with Bayes factors, but each approach faces difficulties that we briefly review. In the current context of multiple studies on different genotyping platforms, we argue for the use of truly genome-wide significance thresholds, based on all polymorphisms whether or not typed in the study. We approximate genome-wide significance thresholds in contemporary West African, East Asian and European populations by simulating sequence data, based on all polymorphisms a..