Mapping the regulatory genetic landscape of complex traits using a chicken advanced intercross line

Complex traits exhibit a highly polygenic architecture that complicates gene mapping and molecular characterization. As a model organism for birds, chickens possess high-quality reference panels, functional annotations, and molecular quantitative trait locus maps. However, the genetic mechanisms underlying growth traits have not been systematically analyzed. Here, we develop a 16-generation advanced intercross line of chickens to enhance informative recombination and identify 154 single-gene quantitative trait loci. We use multiple co-localization methods to establish a network landscape of tissue-specific regulatory mutations and functional gene relationships. We leverage gene-clustering and restoration quantitative trait loci within the omnigenic model framework to elucidate the genetic regulation system of growth traits. Cross-species comparisons show the conserved functions of growth-related genes and divergent features of regulatory mechanisms in mammals and birds.