Comprehensive Multi-omics Analysis of Regulatory Variants for Body Weight in Cattle.

Abstract

Body weight is a polygenic trait with intricate inheritance patterns. Functional genomics enriched with multi-layer annotations offers essential resources for exploring the genetic architecture of complex traits. In this study, we undertook an extensive characterization of regulatory variants for body weight related traits in cattle using a multi-omics approach. First, we identified seven candidate genes through an integrative analysis of selective sweeps and multiple genome-wide association studies (GWAS) strategies using imputed whole-genome sequencing in a population of 1577 individuals. Subsequently, we uncovered 3340 eGenes [genes whose expression levels are significantly associated with genetic variants in expression quantitative trait locus (eQTL) studies] across 227 muscle samples. Transcriptome-wide association studies (TWAS) further revealed a total of 532 distinct candidate genes associated with body weight traits. Also, colocalization analyses unveiled 44 genes that were shared between eQTLs and GWAS. Moreover, our comprehensive analysis highlighted one target genomic region under positive selection with pleiotropic genes (LAP3, MED28, and NCAPG), and pinpointed a prioritized functional variant within the locus on Bos taurus autosome 6 (BTA6) with complex regulation for body weight by integrating GWAS, selective sweep, eQTL, TWAS, as well as epigenomic analysis and molecular validation. Additionally, convergent evolution analysis and phenome-wide association studies underscored the conservation of the locus across species. Our study provided a comprehensive understanding of the genetic regulation for body weight related traits through multi-omics analysis in cattle. Our findings contribute to unraveling the genetic mechanisms governing weight related traits and shed valuable light on the genetic improvement of farm animals.