Integrated Multi‐Omics Analysis Reveals the Genetic Basis of Phenotypic Variation in Tibetan Sheep

Body size is a key economic trait influencing the profitability of farmed animals. This study used genome-wide association studies (GWAS) to identify five single nucleotide polymorphisms (SNPs) significantly associated with body size in the Tibetan sheep population, advancing molecular breeding and providing a basis for genomic selection. These SNPs are located within five candidate genes. SNaPshot validated GWAS results, demonstrating significant correlations between candidate SNPs and body size traits in Tibetan sheep. Concurrently, hematoxylin and eosin staining, alongside muscle fiber analysis, confirmed pronounced morphological differences in muscle tissue between sheep of varying conformation. Therefore, transcriptome and proteomics were performed on the longest dorsi muscle from large and small Tibetan sheep of both sexes. The transcriptome, together with weighted gene co-expression network analysis (WGCNA), identified VEPH1 and PRKG1 as core genes regulating body characteristics in Tibetan sheep through their involvement in the PI3K-Akt signaling pathway and pathways related to fat deposition. The integrative analyses demonstrated significantly different expression of CARNS1 and CRYAB at both transcriptional and protein levels between the muscles of large- and small-sized Tibetan sheep of both sexes, suggesting their importance in body size traits by influencing muscle morphology. This study provides valuable genomic resources that advance sheep genetics research.