Epistasis network centrality analysis yields pathway replication across two GWAS cohorts for bipolar disorder.

ABSTRACT: Most pathway and gene-set enrichment methods prioritize genes by their main effect and do not account for variation due to interactions in the pathway. A portion of the presumed missing heritability in genome-wide association studies (GWAS) may be accounted for through gene-gene interactions and additive genetic variability. In this study, we prioritize genes for pathway enrichment in GWAS of bipolar disorder (BD) by aggregating gene-gene interaction information with main effect associations through a machine learning (evaporative cooling) feature selection and epistasis network centrality analysis. We validate this approach in a two-stage (discovery/replication) pathway analysis of GWAS of BD. The discovery cohort comes from the Wellcome Trust Case Control Consortium (WTCCC) GWAS of BD, a

SUBMITTER: Pandey A 

PROVIDER: S-EPMC3432194 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature