Integrative analyses of genomic and metabolomic data reveal genetic mechanisms associated with carcass merit traits in beef cattle

Abstract

Improvement of carcass merit traits is a priority for the beef industry. Discovering DNA variants and genes associated with variation in these traits and understanding biological functions/processes underlying their associations are of paramount importance for more effective genetic improvement of carcass merit traits in beef cattle. This study integrates 10,488,742 imputed whole genome DNA variants, 31 plasma metabolites, and animal phenotypes to identify genes and biological functions/processes that are associated with carcass merit traits including hot carcass weight (HCW), rib eye area (REA), average backfat thickness (AFAT), lean meat yield (LMY), and carcass marbling score (CMAR) in a population of 493 crossbred beef cattle. Regression analyses were performed to identify plasma metabolites associated with the carcass merit traits, and the results showed that 4 (3-hydroxybutyric acid, acetic acid, citric acid, and choline), 6 (creatinine, L-glutamine, succinic acid, pyruvic acid, L-lactic acid, and 3-hydroxybutyric acid), 4 (fumaric acid, methanol, D-glucose, and glycerol), 2 (L-lactic acid and creatinine), and 5 (succinic acid, fumaric acid, lysine, glycine, and choline) plasma metabolites were significantly associated with HCW, REA, AFAT, LMY, and CMAR (P-value < 0.1), respectively. Combining the results of metabolome-genome wide association studies using the 10,488,742 imputed SNPs, 103, 160, 83, 43, and 109 candidate genes were identified as significantly associated with HCW, REA, AFAT, LMY, and CMAR (P-value < 1 × 10^-5), respectively. By applying functional enrichment analyses for candidate genes of each trait, 26, 24, 26, 24, and 28 significant cellular and molecular functions were predicted for HCW, REA, AFAT, LMY, and CMAR, respectively. Among the five topmost significantly enriched biological functions for carcass merit traits, molecular transport and small molecule biochemistry were two top biological functions associated with all carcass merit traits. Lipid metabolism was the most significant biological function for LMY and CMAR and it was also the second and fourth highest biological function for REA and HCW, respectively. Candidate genes and enriched biological functions identified by the integrative analyses of metabolites with phenotypic traits and DNA variants could help interpret the results of previous genome-wide association studies for carcass merit traits. Our integrative study also revealed additional potential novel genes associated with these economically important traits. Therefore, our study improves understanding of the molecular and biological functions/processes that influence carcass merit traits, which could help develop strategies to enhance genomic prediction of carcass merit traits with incorporation of metabolomic data. Similarly, this information could guide management practices, such as nutritional interventions, with the purpose of boosting specific carcass merit traits.