Integrating large-scale meta-GWAS and PigGTEx resources to decipher the genetic basis of 232 complex traits in pigs

作者：Zhiting Xu, Qing Lin, Xiaodian Cai, Zhanming Zhong, Jinyan Teng, Bingjie Li, Haonan Zeng, Yahui Gao, Zexi Cai, Xiaoqing Wang, Liangyu Shi, Xue Wang, Yi Wang, Zipeng Zhang, Zipeng Zhang, Yu Lin, Shuli Liu, Hongwei Yin, Zhonghao Bai, Chen Wei, Jun Zhou, Xiaoke Zhang, Xiaoke Zhang, Shaolei Shi, Jun Wu, Shuqi Diao, Yuqiang Liu, Xiangchun Pan, Xueyan Feng, Ruiqi Liu, Zhanqin Su, Chengjie Chang, Qianghui Zhu, Yuwei Wu, Zhou Zhongyin, Lijing Bai, Kui Li, Qishan Wang, Yuchun Pan, Zhong Xu, Xianwen Peng, Shuqi Mei, Delin Mo, Xiaohong Liu, Hao Zhang, Xiaolong Yuan, George E. Liu, Guosheng Su, Guosheng Su, Goutam Sahana, Mogens Sandø Lund, Li Ma, Ruidong Xiang, Xia Shen, Pinghua Li, Ruihua Huang, Maria Ballester, Daniel Crespo‐Piazuelo, Marcel Amills, Alex Clop, Peter Karlskov‐Mortensen, Merete Fredholm, Guoqing Tang, Xuewei Li, Xuewei Li, Xiangdong Ding, Jiaqi Li, Yaosheng Chen, Qin Zhang, Fuping Zhao, Fuping Zhao, Lingzhao Fang, Zhe Zhang, Zhe Zhang · 发表于：National Science Review · 年份：2025 · DOI：10.1093/nsr/nwaf048 · 被引用次数：24 · 研究领域：Genetic and phenotypic traits in livestock、Genetic Mapping and Diversity in Plants and Animals、Cancer-related molecular mechanisms research

ABSTRACT Understanding the molecular and cellular mechanisms underlying complex traits in pigs is crucial for enhancing genetic gain via artificial selection and utilizing pigs as models for human disease and biology. Here, we conducted comprehensive genome-wide association studies (GWAS) followed by a cross-breed meta-analysis for 232 complex traits and a within-breed meta-analysis for 12 traits, using 28.3 million imputed sequence variants in 70 328 animals across 14 pig breeds. We identified 6878 quantitative trait loci (QTL) for 139 complex traits. Leveraging the Pig Genotype-Tissue Expression resource, we systematically investigated the biological context and regulatory mechanisms behind these trait-QTLs, ultimately prioritizing 14 829 variant-gene-tissue-trait regulatory circuits. For instance, rs344053754 regulates UGT2B31 expression in the liver and intestines, potentially by modulating enhancer activity, ultimately influencing litter weight at weaning in pigs. Furthermore, we observed conservation of certain genetic and regulatory mechanisms underlying complex traits between humans and pigs. Overall, our cross-breed meta-GWAS in pigs provides invaluable resources and novel insights into the genetic regulatory and evolutionary mechanisms of complex traits in mammals.