Meta-GWAS of Pig Semen Quality Traits Reveals Conserved Genes Regulating Mammalian Fertility

Semen quality serves as a vital indicator of male fertility, yet its underlying genetic and regulatory mechanisms remain poorly understood. Here, 1.15 million records of six semen quality traits from 14 210 boars in four distinct breeds were collected. These traits have low to moderate heritability (0.12-0.26), and are genetically correlated with growth traits like average daily gain. Genome-wide association study (GWAS) and multi-breed meta-analysis detected 234 loci associated with semen quality. Systematic integration of the Pig Genotype-Tissue Expression resource with these GWAS loci allowed the prioritization of 93 causal variants targeting 134 genes. For instance, the expression quantitative trait loci (eQTL) of NAXE in multiple tissues were colocalized with a GWAS loci of the number of sperms, while eQTL of LEFTY2 in the testis was exclusively colocalized with in a GWAS loci of semen volume. Through examining GWAS of semen quality traits in cattle and human complex traits, the ortholog genes (e.g., AURKAIP1 and ADRA2A) significant in pigs also regulated bovine semen quality, and were significantly enriched for heritability of human birth weight and height. This study provides novel insights into semen quality traits in mammals, which will provide candidate genes for pig selective breeding and potential targets for human male infertility research.