Genome-wide Association Studies of Novel Resilience Traits Identify Important Immune QTL Regions and Candidate Genes in Duroc Pigs

Abstract

Resilience traits in pig populations allow animals to deal better with infectious disease and suboptimal production environments. The data on daily weight, feed intake and feed behaviors in pigs are collected in test period by automated feeding stations, which facilitate to evaluate the resilience traits. In this study, we adopted the mean square error roots (RMSE) of ordinary least squares (OLS) and the negative residuals of quantile regression (QR) to generate four different novel resilience traits using daily records of feed intake and feed duration between 90 and 180 days of age in a population of commercial Duroc pigs. The genome-wide association studies (GWAS) based on single- and two- trait mixed models were carried out on 550 pigs using 48,603 single nucleotide polymorphisms (SNPs) to identify genomic regions associated with resilience traits in growing pigs. We further focused on the GWAS signals to conduct gene annotation, colocalization with multi-tissue eQTL summary statistics of PigGTEx project and identification of enhancers and promoters using the publicly available data. The genomic heritabilities of four novel resilience traits ranged from 0.09 to 0.41. The pairwise genetic and phenotypic correlations ranged from 0.16 to 0.95 and from 0.05 to 0.36, respectively. Twenty-seven SNPs were identified to be significantly associated with these resilience traits. They were distributed on nine chromosomes (SSC1, SSC2, SSC6, SSC7, SSC8, SSC12, SSC14, SSC16, and SSC17). After annotation, 39 QTLs and 49 candidate genes were identified. Several of these are functionally relevant candidate genes including OTUD4, TIFA and CARD14, which are involved in the host immune response, disease susceptibility and signal transduction. Eight unique SNPs were found to be causal in both GWAS and eQTL analyses across 15 tissues. Notably, one SNP (rs80794541) was associated with eQTLs identified concurrently across seven tissues/cell types, including the macrophage cell type. Furthermore, four significant SNPs (rs81467127, rs81356029, rs80794541, and rs81305085) were linked to the function of the primed enhancer, active element, and poised promoter in five pig tissues. Using the porcine fibroblast HiC dataset, SNP (rs81356029) on SSC2 regulates the CARNS1 and SSH3, while SNP (rs80794541) on SSC7 regulates the H2AC6. In this study, we generated four novel resilience traits and identified SNPs significantly associated with these resilience traits in a Duroc pig population. GWAS signals were associated with candidate genes involving in the immune traits, and were linked to the crucial regulatory elements as well. Our findings will contribute to elucidating the genetic mechanism that can enhance genome-enabled breeding and inform further research on resilience in domestic pigs.