Integrative analysis of GWAS, epigenomic, and 3D genomic reveals the genetic architecture of body mass index in pigs

Lay Summary Body mass index (BMI) reflects the degree of adiposity and serves as an important indicator for growth and metabolic health. While extensively studied in humans, BMI in pigs is an economically and biologically important trait reflecting body composition, feed efficiency, and metabolic health, yet its genetic basis in pigs remains poorly understood. In this study, we analyzed 4,519 pigs from three commercial breeds (Yorkshire, Landrace, and Duroc) to identify genetic regions affecting body mass index. Through genome-wide association studies (GWAS) we identified several breed-specific loci associated with BMI. To explore how these regions may influence growth and fat deposition, we further integrated histone modifications, chromatin accessibility, and three-dimensional (3D) genomic data from muscle and adipose tissues for functional genomic analyses. By doing this, we pinpointed five quantitative trait loci (QTLs) with potential regulatory functions, and the corresponding candidate genes are closely related to lipid metabolism and muscle development. Two of these loci are orthologous to human and reside within enhancer regions in the human genome, provides suggestive evidence supporting their potential relevance as candidate loci for human traits. These findings reflect breed differences in body composition, provide targets for improving meat production through breeding, and offer insights into genetic mechanisms influencing body weight and metabolism in both pigs and humans.