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

Qunhao Niu; Jiayuan Wu; Tianyi Wu; Tianliu Zhang; Tianzhen Wang; Xu Zheng; Zhida Zhao; Ling Xu; Zezhao Wang; Bo Zhu; Lupei Zhang; Huijiang Gao; Geroge E Liu; Junya Li; Lingyang Xu

doi:10.1093/gpbjnl/qzaf067

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

Genomics Proteomics Bioinformatics. 2025 Aug 18:qzaf067. doi: 10.1093/gpbjnl/qzaf067. Online ahead of print.

Authors

Qunhao Niu¹, Jiayuan Wu¹, Tianyi Wu¹, Tianliu Zhang^{1

2}, Tianzhen Wang¹, Xu Zheng¹, Zhida Zhao¹, Ling Xu³, Zezhao Wang¹, Bo Zhu¹, Lupei Zhang¹, Huijiang Gao¹, Geroge E Liu⁴, Junya Li¹, Lingyang Xu¹

Affiliations

¹ State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
² College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China.
³ School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong Special Administrative Region 999077, China.
⁴ Animal Genomics and Improvement Laboratory, United States Department of Agriculture-Agricultural Research Services, Beltsville, MD 20705, USA.

PMID: 40824217
DOI: 10.1093/gpbjnl/qzaf067

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.

Keywords: Body weight; Cattle; Functional variants; Genetic regulation; Multi-omics.

© The Author(s) 2025. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.