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Title:           Integrating large-scale meta-GWAS and PigGTEx resources to decipher the genetic basis of 232 complex traits in pigs
Subject:         DOI: 10.1093/nsr/nwaf048 National Science Review, 12, 5, 17-02-2025. 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.
Keywords:        pig, meta-GWAS, PigGTEx, molQTL, complex traits
Author:          Xu Zhiting, Lin Qing, Cai Xiaodian, Zhong Zhanming, Teng Jinyan, Li Bingjie, Zeng Haonan, Gao Yahui, Cai Zexi, Wang Xiaoqing, Shi Liangyu, Wang Xue, Wang Yi, Zhang Zipeng, Lin Yu, Liu Shuli, Yin Hongwei, Bai Zhonghao, Wei Chen, Zhou Jun, Zhang Wenjing, Zhang Xiaoke, Shi Shaolei, Wu Jun, Diao Shuqi, Liu Yuqiang, Pan Xiangchun, Feng Xueyan, Liu Ruiqi, Su Zhanqin, Chang Chengjie, Zhu Qianghui, Wu Yuwei,  , Zhou Zhongyin, Bai Lijing, Li Kui, Wang Qishan, Pan Yuchun, Xu Zhong, Peng Xianwen, Mei Shuqi, Mo Delin, Liu Xiaohong, Zhang Hao, Yuan Xiaolong, Liu Yang, Liu George E., Su Guosheng, Sahana Goutam, Lund Mogens Sandø, Ma Li, Xiang Ruidong, Shen Xia, Li Pinghua, Huang Ruihua, Ballester Maria, Crespo-Piazuelo Daniel, Amills Marcel, Clop Alex, Karlskov-Mortensen Peter, Fredholm Merete, Tang Guoqing, Li Mingzhou, Li Xuewei, Ding Xiangdong, Li Jiaqi, Chen Yaosheng, Zhang Qin, Zhao Yunxiang, Zhao Fuping, Fang Lingzhao, Zhang Zhe
Creator:         OUP
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     Item: 
      Title: INTRODUCTION
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     Item: 
      Title: RESULTS
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       Item: 
        Title: Summary of genotypes and phenotypes
        Destination: section*.6
       Item: 
        Title: Sharing patterns of QTL between populations revealed by meta-GWAS
        Destination: section*.8
       Item: 
        Title: Breed specificity and pleiotropy of QTL
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        Title: Functional characterization of GWAS loci by integrating multi-omics data
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        Title: Detecting trait-relevant tissues
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        Title: Exploring shared genetic regulation of complex traits between pigs and humans
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      Title: DISCUSSION
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      Title: MATERIALS AND METHODS
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        Title: Data collection and processing
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       Item: 
        Title: Individual GWAS and quality control
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       Item: 
        Title: Meta-analysis of GWAS
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       Item: 
        Title: Definition and validation of QTL
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      Title: DATA AVAILABILITY
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     Item: 
      Title: SUPPLEMENTARY DATA
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      Title: FUNDING
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    Title: Integrating large-scale meta-GWAS and PigGTEx resources to decipher the genetic basis of 232 complex traits in pigs
    Author: Xu Zhiting, Lin Qing, Cai Xiaodian, Zhong Zhanming, Teng Jinyan, Li Bingjie, Zeng Haonan, Gao Yahui, Cai Zexi, Wang Xiaoqing, Shi Liangyu, Wang Xue, Wang Yi, Zhang Zipeng, Lin Yu, Liu Shuli, Yin Hongwei, Bai Zhonghao, Wei Chen, Zhou Jun, Zhang Wenjing, Zhang Xiaoke, Shi Shaolei, Wu Jun, Diao Shuqi, Liu Yuqiang, Pan Xiangchun, Feng Xueyan, Liu Ruiqi, Su Zhanqin, Chang Chengjie, Zhu Qianghui, Wu Yuwei,  , Zhou Zhongyin, Bai Lijing, Li Kui, Wang Qishan, Pan Yuchun, Xu Zhong, Peng Xianwen, Mei Shuqi, Mo Delin, Liu Xiaohong, Zhang Hao, Yuan Xiaolong, Liu Yang, Liu George E., Su Guosheng, Sahana Goutam, Lund Mogens Sandø, Ma Li, Xiang Ruidong, Shen Xia, Li Pinghua, Huang Ruihua, Ballester Maria, Crespo-Piazuelo Daniel, Amills Marcel, Clop Alex, Karlskov-Mortensen Peter, Fredholm Merete, Tang Guoqing, Li Mingzhou, Li Xuewei, Ding Xiangdong, Li Jiaqi, Chen Yaosheng, Zhang Qin, Zhao Yunxiang, Zhao Fuping, Fang Lingzhao, Zhang Zhe
    Subject: DOI: 10.1093/nsr/nwaf048 National Science Review, 12, 5, 17-02-2025. 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.
    Keywords: pig, meta-GWAS, PigGTEx, molQTL, complex traits
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               <rdf:li>Xu Zhiting</rdf:li>
               <rdf:li>Lin Qing</rdf:li>
               <rdf:li>Cai Xiaodian</rdf:li>
               <rdf:li>Zhong Zhanming</rdf:li>
               <rdf:li>Teng Jinyan</rdf:li>
               <rdf:li>Li Bingjie</rdf:li>
               <rdf:li>Zeng Haonan</rdf:li>
               <rdf:li>Gao Yahui</rdf:li>
               <rdf:li>Cai Zexi</rdf:li>
               <rdf:li>Wang Xiaoqing</rdf:li>
               <rdf:li>Shi Liangyu</rdf:li>
               <rdf:li>Wang Xue</rdf:li>
               <rdf:li>Wang Yi</rdf:li>
               <rdf:li>Zhang Zipeng</rdf:li>
               <rdf:li>Lin Yu</rdf:li>
               <rdf:li>Liu Shuli</rdf:li>
               <rdf:li>Yin Hongwei</rdf:li>
               <rdf:li>Bai Zhonghao</rdf:li>
               <rdf:li>Wei Chen</rdf:li>
               <rdf:li>Zhou Jun</rdf:li>
               <rdf:li>Zhang Wenjing</rdf:li>
               <rdf:li>Zhang Xiaoke</rdf:li>
               <rdf:li>Shi Shaolei</rdf:li>
               <rdf:li>Wu Jun</rdf:li>
               <rdf:li>Diao Shuqi</rdf:li>
               <rdf:li>Liu Yuqiang</rdf:li>
               <rdf:li>Pan Xiangchun</rdf:li>
               <rdf:li>Feng Xueyan</rdf:li>
               <rdf:li>Liu Ruiqi</rdf:li>
               <rdf:li>Su Zhanqin</rdf:li>
               <rdf:li>Chang Chengjie</rdf:li>
               <rdf:li>Zhu Qianghui</rdf:li>
               <rdf:li>Wu Yuwei</rdf:li>
               <rdf:li> </rdf:li>
               <rdf:li>Zhou Zhongyin</rdf:li>
               <rdf:li>Bai Lijing</rdf:li>
               <rdf:li>Li Kui</rdf:li>
               <rdf:li>Wang Qishan</rdf:li>
               <rdf:li>Pan Yuchun</rdf:li>
               <rdf:li>Xu Zhong</rdf:li>
               <rdf:li>Peng Xianwen</rdf:li>
               <rdf:li>Mei Shuqi</rdf:li>
               <rdf:li>Mo Delin</rdf:li>
               <rdf:li>Liu Xiaohong</rdf:li>
               <rdf:li>Zhang Hao</rdf:li>
               <rdf:li>Yuan Xiaolong</rdf:li>
               <rdf:li>Liu Yang</rdf:li>
               <rdf:li>Liu George E.</rdf:li>
               <rdf:li>Su Guosheng</rdf:li>
               <rdf:li>Sahana Goutam</rdf:li>
               <rdf:li>Lund Mogens Sandø</rdf:li>
               <rdf:li>Ma Li</rdf:li>
               <rdf:li>Xiang Ruidong</rdf:li>
               <rdf:li>Shen Xia</rdf:li>
               <rdf:li>Li Pinghua</rdf:li>
               <rdf:li>Huang Ruihua</rdf:li>
               <rdf:li>Ballester Maria</rdf:li>
               <rdf:li>Crespo-Piazuelo Daniel</rdf:li>
               <rdf:li>Amills Marcel</rdf:li>
               <rdf:li>Clop Alex</rdf:li>
               <rdf:li>Karlskov-Mortensen Peter</rdf:li>
               <rdf:li>Fredholm Merete</rdf:li>
               <rdf:li>Tang Guoqing</rdf:li>
               <rdf:li>Li Mingzhou</rdf:li>
               <rdf:li>Li Xuewei</rdf:li>
               <rdf:li>Ding Xiangdong</rdf:li>
               <rdf:li>Li Jiaqi</rdf:li>
               <rdf:li>Chen Yaosheng</rdf:li>
               <rdf:li>Zhang Qin</rdf:li>
               <rdf:li>Zhao Yunxiang</rdf:li>
               <rdf:li>Zhao Fuping</rdf:li>
               <rdf:li>Fang Lingzhao</rdf:li>
               <rdf:li>Zhang Zhe</rdf:li>
            </rdf:Seq>
         </dc:contributor>
         <dc:publisher>
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               <rdf:li>Oxford University Press</rdf:li>
            </rdf:Bag>
         </dc:publisher>
         <dc:description>
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               <rdf:li xml:lang="x-default">DOI: 10.1093/nsr/nwaf048 National Science Review, 12, 5, 17-02-2025. 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&amp;#x2009;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&amp;#x2009;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.</rdf:li>
            </rdf:Alt>
         </dc:description>
         <dc:subject>
            <rdf:Bag>
               <rdf:li>pig</rdf:li>
               <rdf:li>meta-GWAS</rdf:li>
               <rdf:li>PigGTEx</rdf:li>
               <rdf:li>molQTL</rdf:li>
               <rdf:li>complex traits</rdf:li>
            </rdf:Bag>
         </dc:subject>
         <dc:title>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">Integrating large-scale meta-GWAS and PigGTEx resources to decipher the genetic basis of 232 complex traits in pigs</rdf:li>
            </rdf:Alt>
         </dc:title>
         <dc:creator>
            <rdf:Seq>
               <rdf:li>Xu Zhiting, Lin Qing, Cai Xiaodian, Zhong Zhanming, Teng Jinyan, Li Bingjie, Zeng Haonan, Gao Yahui, Cai Zexi, Wang Xiaoqing, Shi Liangyu, Wang Xue, Wang Yi, Zhang Zipeng, Lin Yu, Liu Shuli, Yin Hongwei, Bai Zhonghao, Wei Chen, Zhou Jun, Zhang Wenjing, Zhang Xiaoke, Shi Shaolei, Wu Jun, Diao Shuqi, Liu Yuqiang, Pan Xiangchun, Feng Xueyan, Liu Ruiqi, Su Zhanqin, Chang Chengjie, Zhu Qianghui, Wu Yuwei,  , Zhou Zhongyin, Bai Lijing, Li Kui, Wang Qishan, Pan Yuchun, Xu Zhong, Peng Xianwen, Mei Shuqi, Mo Delin, Liu Xiaohong, Zhang Hao, Yuan Xiaolong, Liu Yang, Liu George E., Su Guosheng, Sahana Goutam, Lund Mogens Sandø, Ma Li, Xiang Ruidong, Shen Xia, Li Pinghua, Huang Ruihua, Ballester Maria, Crespo-Piazuelo Daniel, Amills Marcel, Clop Alex, Karlskov-Mortensen Peter, Fredholm Merete, Tang Guoqing, Li Mingzhou, Li Xuewei, Ding Xiangdong, Li Jiaqi, Chen Yaosheng, Zhang Qin, Zhao Yunxiang, Zhao Fuping, Fang Lingzhao, Zhang Zhe</rdf:li>
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  Checksum: 7a439cae
   Type: CRC32
  Checksum: 67b7df26acf1b9b5b8cead8e2397ff41
   Type: MD5
  Checksum: d9953fbd5f789d87eefc7c077bbed8b8c32c4078
   Type: SHA-1
  Checksum: 207b8c6641cb424f3894b0fc8c1c70763ac3ffa0a23925bdbf42e657057e259a
   Type: SHA-256