Decoding the spatial regulatory architecture of avian adiposity reveals an ADM-centered paracrine relay driven by a selected distal enhancer

Ducks represent an exceptional biological model for studying fat deposition due to their unique metabolic efficiency. However, the genetic "dark matter"—non-coding variants—has long obscured the precise regulatory mechanisms that GWAS alone cannot resolve. In this study, we decoded the regulatory architecture of duck adiposity by integrating epigenomic, 3D genomic, and transcriptomic landscapes across divergent duck lines. By pioneering a "mixed-strategy" gene prioritization—combining WGCNA with a Bayesian framework—we successfully narrowed down millions of variants to 116 high-confidence candidate genes. Most notably, we unmasked a master regulatory switch: a key functional SNP that modulates ADM expression by reshaping chromatin accessibility and enhancer activity, specifically through the recruitment of SMAD2. Relevant evidences indicate that ADM acts as a paracrine signal, driving a cellular "dialogue" that stimulates the proliferation and differentiation of neighboring preadipocytes. This work not only provides a high-resolution map of the duck epigenome but also offers a precision blueprint for genetic selection in poultry breeding.