Protein-protein interactions shape trans-regulatory impact of genetic variation on protein expression and complex traits.

ABSTRACT: Most genetic variants influence complex traits by affecting gene regulation. Yet, despite comprehensive catalogs of molecular quantitative trait loci (QTLs), linking trait-associated variants to biological functions remains difficult. By re-analyzing large maps of protein QTLs (pQTLs), we found that genes with trans-pQTLs but no cis-pQTLs are under strong selective constraints and are particularly informative in interpreting genome-wide association study (GWAS) loci. We observed that trans-pQTLs and their target proteins are frequently involved in protein-protein interactions (PPIs). Notably, trans-pQTLs are enriched in missense variants and at PPI interfaces, suggesting a key role of PPIs in the trans-regulation of proteome. Using PPI annotations to guide trans-pQTL mapping, we identified

SUBMITTER: Li J 

PROVIDER: S-EPMC12807863 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature