Integrative multi-omics analysis identifies GNAZ and SLC5A4 as critical regulators of gestation length in Large White pigs

As a key index of reproductive performance in pigs, gestation length (GL) exerts a direct influence on litter size and the survival rate of piglets. Phenotypic variability in GL has been observed across Large White pig populations. To elucidate the genetic mechanisms underlying GL, this study analyzed 22,783 reproductive records from 9,057 pigs across five Large White populations. We employed a combination of diverse analytical strategies, encompassing genome-wide association studies (GWAS), GWAS meta-analysis, Bayesian fine-mapping (BFM), transcriptome-wide association studies (TWAS), phenome-wide association studies (PheWAS), and epigenetic profiling.

GWAS and meta-analysis identified multiple novel GL-associated genomic regions on Sus scrofa chromosomes (SSC) 2, 7, 9, and 14. BFM refined the confidence intervals of these quantitative trait loci (QTLs), narrowing them to 10,460,892–10,737,692 bp and 31,384,086–31,384,333 bp on SSC7:, to 127,322,114–128,205,369 bp on SSC9:, and to 24,640,681–25,479,574 bp on SSC12:. TWAS revealed significant GL-related gene expression changes in relevant tissues, identifying GNAZ and SLC5A4—both located within the fine-mapped QTL on SSC14 (48.25–49.02 Mb)—as key regulators of GL. PheWAS further validated the association of GNAZ and SLC5A4 with GL, while epigenetic profiling showed active chromatin states and broad promoter activity at the GNAZ locus, supporting its regulatory potential.

Through multi-omics integration, this study pinpoints GNAZ and SLC5A4 as core functional candidate genes regulating GL in Large White pigs. These results yield new perspectives on the genetic underpinnings governing porcine GL and supply valuable genetic materials for enhancing reproductive performance in swine breeding initiatives.