Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures.

ABSTRACT: Genetic variants identified by genome-wide association studies explain only a modest proportion of heritability, suggesting that meaningful associations lie 'hidden' below current thresholds. Here, we integrate information from association studies with epigenomic maps to demonstrate that enhancers significantly overlap known loci associated with the cardiac QT interval and QRS duration. We apply functional criteria to identify loci associated with QT interval that do not meet genome-wide significance and are missed by existing studies. We demonstrate that these 'sub-threshold' signals represent novel loci, and that epigenomic maps are effective at discriminating true biological signals from noise. We experimentally validate the molecular, gene-regulatory, cellular and organismal phenotypes

SUBMITTER: Wang X 

PROVIDER: S-EPMC4862755 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature