Local Joint Testing Improves Power and Identifies Hidden Heritability in Association Studies.

ABSTRACT: There is mounting evidence that complex human phenotypes are highly polygenic, with many loci harboring multiple causal variants, yet most genetic association studies examine each SNP in isolation. While this has led to the discovery of thousands of disease associations, discovered variants account for only a small fraction of disease heritability. Alternative multi-SNP methods have been proposed, but issues such as multiple-testing correction, sensitivity to genotyping error, and optimization for the underlying genetic architectures remain. Here we describe a local joint-testing procedure, complete with multiple-testing correction, that leverages a genetic phenomenon we call linkage masking wherein linkage disequilibrium between SNPs hides their signal under standard association methods.

SUBMITTER: Brown BC 

PROVIDER: S-EPMC4937483 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature