Integrating large-scale meta-GWAS and PigGTEx resources to decipher the genetic basis of complex traits in pig.
Xu, Z.; Lin, Q.; Cai, X.; Zhong, Z.; Li, B.; Teng, J.; 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.; The PigGTEx Consortium, ; 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, G. E.; Su, G.; Sahana, G.; Lund, M.; Ma, L.; Xiang, R.; Shen, X.; Li, P.; Huang, R.; Ballester, M.; Crespo-Piazuelo, D.; Amills, M.; Clop,
Show abstract
Understanding the molecular and cellular mechanisms that underlie complex traits in pigs is crucial for enhancing their genetic improvement program and unleashing their substantial potentials in human biomedicine research. Here, we conducted a meta-GWAS analysis for 232 complex traits with 28.3 million imputed whole-genome sequence variants in 70,328 individuals from 14 pig breeds. We identified a total of 6,878 genomic regions associated with 139 complex traits. By integrating with the Pig Genotype-Tissue Expression (PigGTEx) resource, we systemically explored the biological context and regulatory circuits through which these trait-associated variants act and finally prioritized 16,664 variant-gene-tissue-trait circuits. For instance, rs344053754 regulates the expression of UGT2B31 in the liver by affecting the activity of regulatory elements and ultimately influences litter weight at weaning. Furthermore, we investigated the conservation of genetic and regulatory mechanisms underlying 136 human traits and 232 pig traits. Overall, our multi-breed meta-GWAS in pigs provides invaluable resources and novel insights for understanding the regulatory and evolutionary mechanisms of complex traits in both pigs and humans.
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