Integrative genomic analyses dissect the genetic architecture of gestation length in pigs

Gestation length (GL) is a crucial reproductive trait in pigs that influences neonatal survival and overall sow productivity; however, its underlying genetic architecture remains mainly undefined due to limited statistical power in previous studies. To address this, we conducted a large-scale cross-population genome-wide association studies (meta-GWAS) for GL, leveraging 30,140 phenotypic records from 10,484 pigs across 11 populations spanning Duroc, Landrace, and Yorkshire breeds. After quality control, 18,966,522 SNPs were available for meta-analysis. We identified 3,480 associated SNPs in 34 quantitative trait loci (QTLs) meeting the significant threshold ( \(\:P\:<\:{10}⁻⁵\) ). Post-GWAS analyses, including BayesS, revealed that GL is a highly polygenic trait ( \(\:{{h}}²≈\:0.19\) , range: 0.06–0.59, \(\:{π\:}≈\:7.4%\) ) with an allele-frequency–effect-size relationship consistent with negative selection ( \(\:{S}≈\:-2.18\) ). GL-associated variants are disproportionately located in non-coding regulatory elements, particularly active enhancers and weak Polycomb-repressed regions, and highly enriched in the fetal thymus, muscle, morula, placenta, and uterus ( \(\:P\:<\:0.05\) ). Through an integrative systems genetics approach combining transcriptome-wide association study (TWAS), summary-data-based Mendelian randomization (SMR), colocalization, and MAGMA using PigGTEx data, we prioritized multiple effector genes. Notably, SSTR1 on SSC7 was supported by all five evidence layers, linking GL variation to hormonal control of myometrial contractility. Other candidate genes, including RASGRP4 , TMEM131L , SNX14 , and PPP1R14A , were implicated in uterine signaling and immune regulation. These findings refine the genetic understanding of porcine gestation length and provide robust molecular targets for future functional investigation and breeding research.