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

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; Yu Lin; Shuli Liu; Hongwei Yin; Zhonghao Bai; Chen Wei; Jun Zhou; Wenjing 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; Zhongyin Zhou; Lijing Bai; Kui Li; Qishan Wang; Yuchun Pan; Zhong Xu; Xianwen Peng; Shuqi Mei; Delin Mo; Xiaohong Liu; Hao Zhang; Xiaolong Yuan; Yang Liu; George E. Liu; 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; Mingzhou Li; Xuewei Li; Xiangdong Ding; Jiaqi Li; Yaosheng Chen; Qin Zhang; Yunxiang Zhao; Fuping Zhao; Lingzhao Fang; Zhe Zhang

doi:10.1093/nsr/nwaf048

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

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, Yu Lin, Shuli Liu, Hongwei Yin, Zhonghao Bai, Chen Wei, Jun ZhouWenjing 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, Zhongyin Zhou, Lijing Bai, Kui Li, Qishan Wang, Yuchun Pan, Zhong Xu, Xianwen Peng, Shuqi Mei, Delin Mo, Xiaohong Liu, Hao Zhang, Xiaolong Yuan, Yang Liu, George E. Liu, 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, Mingzhou Li, Xuewei Li, Xiangdong Ding, Jiaqi Li, Yaosheng Chen, Qin Zhang, Yunxiang Zhao^*, Fuping Zhao^*, Lingzhao Fang^*, Zhe Zhang^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

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.

Original language	English
Article number	nwaf048
Journal	National Science Review
Volume	12
Issue number	5
Early online date	17 Feb 2025
DOIs	https://doi.org/10.1093/nsr/nwaf048
Publication status	Print publication - 1 May 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

Keywords

complex traits
meta-GWAS
molQTL
pig
PigGTEx

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/nsr/nwaf048

nwaf048Final published version, 45.5 MBLicence: CC BY

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Xu, Z., Lin, Q., Cai, X., Zhong, Z., Teng, J., Li, B., Zeng, H., Gao, Y., Cai, Z., Wang, X., Shi, L., Wang, X., Wang, Y., Zhang, Z., Lin, Y., Liu, S., Yin, H., Bai, Z., Wei, C., ... Zhang, Z. (2025). Integrating large-scale meta-GWAS and PigGTEx resources to decipher the genetic basis of 232 complex traits in pigs. National Science Review, 12(5), Article nwaf048. https://doi.org/10.1093/nsr/nwaf048

@article{b88cd0868b564f79bcabc8e00289cd0d,

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

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 = "complex traits, meta-GWAS, molQTL, pig, PigGTEx",

author = "Zhiting Xu and Qing Lin and Xiaodian Cai and Zhanming Zhong and Jinyan Teng and Bingjie Li and Haonan Zeng and Yahui Gao and Zexi Cai and Xiaoqing Wang and Liangyu Shi and Xue Wang and Yi Wang and Zipeng Zhang and Yu Lin and Shuli Liu and Hongwei Yin and Zhonghao Bai and Chen Wei and Jun Zhou and Wenjing Zhang and Xiaoke Zhang and Shaolei Shi and Jun Wu and Shuqi Diao and Yuqiang Liu and Xiangchun Pan and Xueyan Feng and Ruiqi Liu and Zhanqin Su and Chengjie Chang and Qianghui Zhu and Yuwei Wu and Zhongyin Zhou and Lijing Bai and Kui Li and Qishan Wang and Yuchun Pan and Zhong Xu and Xianwen Peng and Shuqi Mei and Delin Mo and Xiaohong Liu and Hao Zhang and Xiaolong Yuan and Yang Liu and Liu, \{George E.\} and Guosheng Su and Goutam Sahana and Lund, \{Mogens Sand{\o}\} and Li Ma and Ruidong Xiang and Xia Shen and Pinghua Li and Ruihua Huang and Maria Ballester and Daniel Crespo-Piazuelo and Marcel Amills and Alex Clop and Peter Karlskov-Mortensen and Merete Fredholm and Guoqing Tang and Mingzhou Li and Xuewei Li and Xiangdong Ding and Jiaqi Li and Yaosheng Chen and Qin Zhang and Yunxiang Zhao and Fuping Zhao and Lingzhao Fang and Zhe Zhang",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = may,

day = "1",

doi = "10.1093/nsr/nwaf048",

language = "English",

volume = "12",

journal = "National Science Review",

issn = "2095-5138",

publisher = "Oxford University Press",

number = "5",

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Xu, Z, Lin, Q, Cai, X, Zhong, Z, Teng, J, Li, B, Zeng, H, Gao, Y, Cai, Z, Wang, X, Shi, L, Wang, X, Wang, Y, Zhang, Z, Lin, Y, Liu, S, Yin, H, Bai, Z, Wei, C, Zhou, J, Zhang, W, Zhang, X, Shi, S, Wu, J, Diao, S, Liu, Y, Pan, X, Feng, X, Liu, R, Su, Z, Chang, C, Zhu, Q, Wu, Y, Zhou, Z, Bai, L, Li, K, Wang, Q, Pan, Y, Xu, Z, Peng, X, Mei, S, Mo, D, Liu, X, Zhang, H, Yuan, X, Liu, Y, Liu, GE, Su, G, Sahana, G, Lund, MS, Ma, L, Xiang, R, Shen, X, Li, P, Huang, R, Ballester, M, Crespo-Piazuelo, D, Amills, M, Clop, A, Karlskov-Mortensen, P, Fredholm, M, Tang, G, Li, M, Li, X, Ding, X, Li, J, Chen, Y, Zhang, Q, Zhao, Y, Zhao, F, Fang, L & Zhang, Z 2025, 'Integrating large-scale meta-GWAS and PigGTEx resources to decipher the genetic basis of 232 complex traits in pigs', National Science Review, vol. 12, no. 5, nwaf048. https://doi.org/10.1093/nsr/nwaf048

TY - JOUR

T1 - Integrating large-scale meta-GWAS and PigGTEx resources to decipher the genetic basis of 232 complex traits in pigs

AU - Xu, Zhiting

AU - Lin, Qing

AU - Cai, Xiaodian

AU - Zhong, Zhanming

AU - Teng, Jinyan

AU - Li, Bingjie

AU - Zeng, Haonan

AU - Gao, Yahui

AU - Cai, Zexi

AU - Wang, Xiaoqing

AU - Shi, Liangyu

AU - Wang, Xue

AU - Wang, Yi

AU - Zhang, Zipeng

AU - Lin, Yu

AU - Liu, Shuli

AU - Yin, Hongwei

AU - Bai, Zhonghao

AU - Wei, Chen

AU - Zhou, Jun

AU - Zhang, Wenjing

AU - Zhang, Xiaoke

AU - Shi, Shaolei

AU - Wu, Jun

AU - Diao, Shuqi

AU - Liu, Yuqiang

AU - Pan, Xiangchun

AU - Feng, Xueyan

AU - Liu, Ruiqi

AU - Su, Zhanqin

AU - Chang, Chengjie

AU - Zhu, Qianghui

AU - Wu, Yuwei

AU - Zhou, Zhongyin

AU - Bai, Lijing

AU - Li, Kui

AU - Wang, Qishan

AU - Pan, Yuchun

AU - Xu, Zhong

AU - Peng, Xianwen

AU - Mei, Shuqi

AU - Mo, Delin

AU - Liu, Xiaohong

AU - Zhang, Hao

AU - Yuan, Xiaolong

AU - Liu, Yang

AU - Liu, George E.

AU - Su, Guosheng

AU - Sahana, Goutam

AU - Lund, Mogens Sandø

AU - Ma, Li

AU - Xiang, Ruidong

AU - Shen, Xia

AU - Li, Pinghua

AU - Huang, Ruihua

AU - Ballester, Maria

AU - Crespo-Piazuelo, Daniel

AU - Amills, Marcel

AU - Clop, Alex

AU - Karlskov-Mortensen, Peter

AU - Fredholm, Merete

AU - Tang, Guoqing

AU - Li, Mingzhou

AU - Li, Xuewei

AU - Ding, Xiangdong

AU - Li, Jiaqi

AU - Chen, Yaosheng

AU - Zhang, Qin

AU - Zhao, Yunxiang

AU - Zhao, Fuping

AU - Fang, Lingzhao

AU - Zhang, Zhe

PY - 2025/5/1

Y1 - 2025/5/1

N2 - 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.

AB - 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.

KW - complex traits

KW - meta-GWAS

KW - molQTL

KW - pig

KW - PigGTEx

UR - https://www.scopus.com/pages/publications/105004546106

U2 - 10.1093/nsr/nwaf048

DO - 10.1093/nsr/nwaf048

M3 - Article

C2 - 40330097

AN - SCOPUS:105004546106

SN - 2095-5138

VL - 12

JO - National Science Review

JF - National Science Review

IS - 5

M1 - nwaf048

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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