Integrating meta-analysis of genome-wide association study with Pig Genotype-Tissue Expression resources uncovers the genetic architecture for age at first farrowing in pigs

Abstract

Age at first farrowing (AFF) is a reproductive trait with low heritability and high importance in the pig industry. To enhance the statistical power of genome-wide association study (GWAS) and further explore the genetic nature of AFF, we first conducted GWAS meta-analysis using three Yorkshire populations, and then integrated the Pig Genotype-Tissue Expression (PigGTEx) resources to interpret their potential regulatory mechanism. Additionally, we compared the AFF in pig with the age at first birth (AFB) of human using GWAS summary statistics. We detected 18 independent variants in GWAS meta-analysis and 8 genes in gene-based association analysis significantly associated with AFF. By integrating the PigGTEx resource, we conducted transcriptome-wide association study (TWAS) and colocalization analysis on 34 pig tissues. In TWAS, we detected 18 significant gene-tissue pairs, such as DCAF6 in uterus and CREG1 in blood. In colocalization, we found 111 potential candidate tissue-gene pairs, such as GJD4 and LYPLAL1. We found that the homologous gene, CHST10, might be the potential candidate gene between humans in AFB and pigs in AFF. In conclusion, integrating GWAS meta-analysis and PigGTEx resources is a meaningful way to decipher the genetic architecture of complex traits. We found that DCAF6, CREG1, GJD4, and LYPLAL1 are candidate genes with high reliability for AFF in swine. The comparative analysis showed that CHST10 might play a potentially critical role in AFB/AFF across human and pigs.