Integrative genomics and regulomics reveal the molecular architecture of complex traits in domestic chickens

Domestic chickens (Gallus gallus domesticus) exhibit exceptional phenotypic diversity and provide a valuable model for studying domestication and artificial selection. We integrated whole-genome resequencing data from ~3000 individuals with 20 slaughter-related traits. Population genomic analyses revealed pronounced genetic differentiation between northern and southern Chinese indigenous chickens, accompanied by distinct signatures of domestication and local adaptation. To dissect the gene regulatory networks of slaughter-related traits, we developed an Integrated Weighted Regulatory Network Analysis (iWRNA) framework that combines genome-wide association signals with multi-tissue transcriptomic and epigenomic data. This approach enabled the identification of tissue-specific regulatory modules and candidate causal genes underlying economically important traits. Notably, liver-weight-associated loci converged on a hepatic metabolic network in which enhancer activity coordinates gene expression and phenotypic variation. These findings establish a comprehensive regulatory atlas for complex trait variation in chickens and provide new insights into the molecular mechanisms of domestication, adaptation, and vertebrate phenotypic evolution.