Transcriptome-wide gene-gene interaction associations elucidate pathways and functional enrichment of complex traits.

ABSTRACT: It remains unknown to what extent gene-gene interactions contribute to complex traits. Here, we introduce a new approach using predicted gene expression to perform exhaustive transcriptome-wide interaction studies (TWISs) for multiple traits across all pairs of genes expressed in several tissue types. Using imputed transcriptomes, we simultaneously reduce the computational challenge and improve interpretability and statistical power. We discover (in the UK Biobank) and replicate (in independent cohorts) several interaction associations, and find several hub genes with numerous interactions. We also demonstrate that TWIS can identify novel associated genes because genes with many or strong interactions have smaller single-locus model effect sizes. Finally, we develop a method to test gene s

SUBMITTER: Evans LM 

PROVIDER: S-EPMC10237671 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature