Integrative GWAS and landscape genomics prioritize candidate loci associated with high-altitude adaptation in Tibetan sheep

High-altitude environments expose Tibetan sheep (Ovis aries) to hypoxia, low temperature, strong ultraviolet radiation, and seasonal nutritional stress. Blood indicators related to immunoglobulins, oxidative stress, and inflammatory cytokines can capture physiological responses to these pressures, but their genetic basis remains incompletely characterized. We integrated whole-genome resequencing data from 220 adult rams across 11 Tibetan sheep populations with 24 blood physiological and biochemical indicators and environmental variables from the sampling sites. A genome-wide association study (GWAS) prioritized 324 candidate SNPs annotated to 310 genes, and genotype-environment association (GEA) analysis detected 121 environment-associated SNPs at a false discovery rate (FDR)<0.05. At the level of non-overlapping 50-kb genomic windows, 27 of 67 environment-associated windows also overlapped with blood trait-associated windows, accounting for 40.30%. Representative candidate genes, including MITF, ANTXR1, FAS, and TTC23L, were associated with blood indicators such as GSH-PX and IgD. Allele-frequency gradients, Bayesian regional prioritization, motif scanning, and public tissue-expression data provided complementary clues for the functional interpretation of the candidate regions. These findings prioritize loci for independent validation and functional studies of high-altitude adaptation in Tibetan sheep.