A genome-wide association study based on plasma high-throughput untargeted metabolomic profiles expands the number of genetically influenced metabolites in pigs

Abstract Metabolomics is a powerful phenomics approach for investigating the molecular mechanisms linking genotype to phenotype and identifying biologically informative traits for precision livestock breeding. However, the genetic architecture of the plasma metabolome remains incompletely characterised in pigs. Here, we investigated the genetic determinism of plasma metabolites in 268 Italian Duroc pigs using untargeted high-throughput metabolomics and genome-wide association analyses. Plasma metabolomic analysis identified 580 quality-controlled metabolites, which were integrated with genotypes from a panel of approximately 60,000 single nucleotide polymorphisms. Heritability estimates indicated moderate genetic contribution on the plasma metabolome, with ~ 46% of metabolites showing heritability greater than 0.20. Overall, 89 metabolite quantitative trait loci (mQTL) regions were identified, involving 156 metabolites and metabolite ratios. Most associations were related to lipid and amino acid metabolism, and several loci harboured biologically plausible candidate genes involved in transport, enzymatic activity, and metabolic regulation. Several mQTL exhibited pleiotropic effects, some metabolites showed evidence of polygenic control, and conditional and ratio-based analyses uncovered additional associations not detected by single-metabolite analyses alone. These findings improve the biological interpretation of metabolic pathways underlying economically relevant traits and support the integration of metabolomics and genomics for precision breeding, feeding, and management strategies in pigs.