327 Beating the heat: Gene network analysis reveal the genetics of thermotolerance in Brangus cattle.

Abstract Heat stress is a major challenge in tropical and subtropical environments, negatively impacting both animal welfare and productivity. This underscores the need for thermotolerant cattle that can maintain internal body temperature and performance under heat-stress conditions. However, phenotypes for selecting thermotolerant and resilient beef cattle remain understudied due to the complex, multi-trait nature of thermotolerance, making genome-wide association studies (GWAS) on individual traits difficult to interpret. To better understand the genetic architecture of thermotolerance, we conducted GWAS followed by gene network analysis to identify key genes, pathways, and functional enrichments associated with thermal resilience. Phenotypic measurements were collected from 3,545 commercial Brangus heifers at the Seminole Tribe of Florida and Williamson Cattle Company from 2016 to 2019. These included five indicators of internal body temperature, four hair length traits, and seven skin properties. All animals were genotyped using a 250K SNP array. GWAS was performed using a mixed linear model association analysis with a leave-one-chromosome-out approach, implemented in GCTA. Significant SNPs were mapped to candidate genes, and gene-wise associations were assessed using an association weight matrix. Thermal stress slope was selected as the key phenotype, with genes harboring at least one significant SNP (P ≤ 0.01) retained for further analysis. Genes were further prioritized if they were associated with at least one additional trait (P ≤ 0.05). Gene network analysis, conducted using Gene Ontology enrichment, revealed key biological processes involved in heat adaptation. Notably, genes related to glycoprotein metabolism and biosynthesis were enriched. Glycoproteins play crucial roles in cell surface interactions, structural integrity, and signaling pathways, facilitating cellular responses to environmental stress. Additionally, pathways associated with calcium-dependent cell-cell adhesion and calcium ion binding were highlighted. Calcium-binding proteins are integral to heat shock responses and cellular adaptation to fluctuating temperatures, making them strong candidates for further thermotolerance research. By integrating GWAS with gene network analysis, this study provides a comprehensive understanding of the genetic basis of thermotolerance in beef cattle. The identified biological processes and molecular pathways offer valuable insights for genomic selection strategies aimed at enhancing heat resilience in cattle populations.