Integrative GWAS, eQTL, and functional validation identify ZNF280B as a key regulator of growth and carcass traits in Hu sheep

Abstract

Hu sheep are a well-known Chinese dual-purpose breed valued for meat production, early sexual maturity, high prolificacy, and adaptability to hot, humid environments. In this study, we combined whole-genome sequencing, GWAS, and eQTL analyses to investigate the genetic basis of growth and slaughter traits in 420 eight-month-old Hu sheep. Using a discovery cohort ( N  = 112) and a validation cohort ( N  = 308), we integrated high-throughput SNP genotyping and RNA sequencing, identifying 559,996 high-quality SNPs and multiple significant loci associated with traits such as live weight and carcass weight. Among the 2,368 cis-eQTLs detected, the most significant was linked to ZNF280B expression in the longissimus lumborum muscle. Functional validation showed that ZNF280B downregulation significantly inhibited skeletal muscle satellite cell proliferation and induced apoptosis, highlighting its critical role in muscle development and fat metabolism. The novelty of this study lies in its large sample size, comprehensive multi-trait analysis, and the integration of functional validation, providing reliable genetic markers for marker-assisted selection in Hu sheep. These findings deepen our understanding of the genetic mechanisms underlying growth and slaughter performance and offer valuable insights for improving production efficiency and promoting sustainable livestock development.