Co-expression-wide association studies link genetically regulated interactions with complex traits.

ABSTRACT: Transcriptome- and proteome-wide association studies (TWAS/PWAS) have proven successful in prioritizing genes and proteins whose genetically regulated expression modulates disease risk, but they ignore potential co-expression and interaction effects. To address this limitation, we introduce the co-expression-wide association study (COWAS) method, which can identify pairs of genes or proteins whose genetically regulated co-expression is associated with complex traits. COWAS first trains models to predict expression and co-expression from genetic variation, and then tests for association between imputed co-expression and the trait of interest while also accounting for direct effects from each exposure. We applied our method to plasma proteomic concentrations from the UK Biobank, identifying

SUBMITTER: Malakhov MM 

PROVIDER: S-EPMC11661334 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature