Exploring the Interplay between the Hologenome and Complex Traits in Bovine and Porcine Animals Using Genome-Wide Association Analysis.

ABSTRACT

Genome-wide association studies (GWAS) significantly enhance our ability to identify trait-associated genomic variants by considering the host genome. Moreover, the hologenome refers to the host organism's collective genetic material and its associated microbiome. In this study, we utilized the hologenome framework, called Hologenome-wide association studies (HWAS), to dissect the architecture of complex traits, including milk yield, methane emissions, rumen physiology in cattle, and gut microbial composition in pigs. We employed four statistical models (1) GWAS, (2) Microbial GWAS (M-GWAS), (3) HWAS-CG (hologenome interaction estimated using COvariance between Random Effects Genome-based restricted maximum likelihood (CORE-GREML)), and (4) HWAS-H (hologenome interaction estimated using the Hadamard product method). We applied Bonferroni correction to interpret the significant associations in the complex traits. The GWAS and M-GWAS detected one and sixteen significant SNPs for milk yield traits, respectively, whereas the HWAS-CG and HWAS-H each identified eight SNPs. Moreover, HWAS-CG revealed four, and the remaining models identified three SNPs each for methane emissions traits. The GWAS and HWAS-CG detected one and three SNPs for rumen physiology traits, respectively. For the pigs' gut microbial composition traits, the GWAS, M-GWAS, HWAS-CG, and HWAS-H identified 14, 16, 13, and 12 SNPs, respectively. We further explored these associations through SNP annotation and by analyzing biological processes and functional pathways. Additionally, we integrated our GWA results with expression quantitative trait locus (eQTL) data using transcriptome-wide association studies (TWAS) and summary-based Mendelian randomization (SMR) methods for a more comprehensive understanding of SNP-trait associations. Our study revealed hologenomic variability in agriculturally important traits, enhancing our understanding of host-microbiome interactions.