Integrated Multi-Omics Analysis Identifies Novel QTLs and Key Candidate Genes Regulating Gestation Length in Large White Pigs

Gestation length (GL) is a critical indicator of reproductive performance in pigs, influencing litter size and piglet survival rates. The mean GL (±SD) for the five Large White pig populations were: PIC (115.99 ± 1.23 days), Topigs (115.43 ± 1.14 days), Danish (116.48 ± 1.22 days), French (114.90 ± 1.22 days), and American (116.22 ± 1.37 days), demonstrating notable phenotypic variability. To elucidate the genetic mechanisms underlying GL, this study systematically identified genetic variants and functional candidate genes associated with GL across five Large White pig populations (comprising 22,783 reproductive records and 9,057 pigs) by integrating genome-wide association studies (GWAS), meta-analysis, Bayesian fine mapping, transcriptome-wide association studies (TWAS), and phenome-wide association studies (pheWAS). Using 50K SNP chip data imputed to whole-genome sequencing (iWGS) level, GWAS and meta-analysis identified multiple novel genomic regions significantly associated with GL on SSC2, SSC7, SSC9, and SSC14. Bayesian fine mapping further refined the confidence intervals of these QTLs, with SSC7: 10,460,892–10,737,692 bp and 31,384,086–31,384,333 bp, SSC9: 127,322,114–128,205,369 bp, and SSC12: 24,640,681–25,479,574 bp. TWAS revealed significant gene expression changes associated with GL in related tissues, identifying GNAZ and SLC5A4 (both residing within the fine-mapped QTL on SSC14 :48.25–49.02 Mb) play pivotal roles in regulating GL. pheWAS further validated the significant association of GNAZ and SLC5A4 with GL. Epigenetic profiling further revealed active chromatin states and broad promoter activity at the GNAZ locus, supporting its regulatory potential. Through multi-omics integration analysis, this study identified GNAZ and SLC5A4 as key functional candidate genes for GL. These findings not only provide novel insights into the genetic mechanisms of GL but also offer valuable genetic resources for improving reproductive performance in pigs.