Joint genetic analysis using variant sets reveals polygenic gene-context interactions

• DOI: 10.1371/journal.pgen.1006693
• Publication Date: 2017-04-20T13:29:16Z
• Authors: Francesco Paolo C...; Danilo Horta; Barbara Rakitsch; Oliver Stegle
• Keywords: Genetic architecture; Trait; Genetic Association

Joint genetic models for multiple traits have helped to enhance association analyses. Most existing multi-trait been designed increase power detecting associations, whereas the analysis of interactions has received considerably less attention. Here, we propose iSet, a method based on linear mixed test between sets variants and environmental states or other contexts. Our model generalizes previous interaction tests in particular provides local differences architecture We first use simulations validate iSet before applying genotype-environment an eQTL study. retrieves larger number than alternative methods reveals that up 20% cases show context-specific configurations causal variants. Finally, apply sub-group specific effects human lipid levels large cohort, where identify gene-sex C-reactive protein is missed by methods.