Combined targeted and untargeted metabolomics in pigs coupled with genomic information: Towards a comprehensive genetic characterization of the pig metabolome

Understanding the biological mechanisms governing the pig metabolism is fundamental for the development of new applications aimed at improving pig production efficiency. Production and reproduction traits are the final result of the molecular mechanisms taking place in an organism, that is the interplay within and between the biological layers encompassing the genome, proteome and metabolome spaces. Thus, the study of each layer allows to deconstruct such complex phenotypes in their small components providing new insights into their biology and additional new simpler phenotypes. Here, we characterized the genome and metabolome spaces to understand the genetic architecture governing the pig metabolism. To this purpose, targeted and untargeted metabolomic platforms were combined to analyze the abundance of more than 1000 plasma metabolites in about 1300 heavy pigs, including 900 Italian Large White and 400 Italian Duroc pigs, that were genotyped with a high-density SNP panel. For each breed, metabolomics profiles were used to study the metabolite-metabolite relationships via a network approach. The networks reconstructed for both breeds resulted similar, though differences emerged, with poorly interconnected modules. Then, metabolomics and genomics data were coupled to study the effect of genome variability over the metabolome via genome-wide association studies (GWAS). Different genomic scans were carried out, including single-marker and haplotype-based analysis of both single metabolites and metabolite ratios. Moreover, whole-genome sequencing data were used for the identification of putative causative mutations. GWAS analyses allowed to detect several quantitative trait loci, most of them including genomic regions carrying enzyme-encoding genes known to control the analyzed metabolites. Overall, we obtained for the first time a comprehensive catalog of genes and variants linked to the pig metabolism, opening new scenarios for the improvement of pig production systems.