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Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries

2023; Nature Portfolio; Volume: 55; Issue: 5 Linguagem: Inglês

10.1038/s41588-023-01384-0

1546-1718

Zhanju Liu, Ruize Liu, Han Gao, Seulgi Jung, Xiang Gao, Ruicong Sun, Xiaoming Liu, Yong‐Jae Kim, Ho‐Su Lee, Yosuke Kawai, Masao Nagasaki, Junji Umeno, Katsushi Tokunaga, Yoshitaka Kinouchi, Atsushi Masamune, Wenzhao Shi, Chengguo Shen, Zhenglin Guo, Kai Yuan, María T. Abreu, Jean‐Paul Achkar, Vibeke Andersen, Çharles N. Bernstein, Steven R. Brant, Luís Bujanda, Siew C. Ng, Lee A. Denson, Richard H. Duerr, Lynnette R. Ferguson, Denis Franchimont, André Franke, Richard B. Gearry, Hákon Hákonarson, Jonas Halfvarson, Caren Heller, Antonio Julià, Judith R. Kelsen, Hamed Khalili, S. Kugathasan, Juozas Kupčinskas, Anna Latiano, Édouard Louis, Reza Malekzadeh, Jacob L. McCauley, Christopher J. Moran, David Okou, Tim Orchard, Aarno Palotie, Miles Parkes, Joel Pekow, Uroš Potočnik, Graham L. Radford‐Smith, John D. Rioux, Gerhard Rogler, Bruce E. Sands, Mark S. Silverberg, Harry Sokol, Séverine Vermeire, Rinse K. Weersma, Ramnik J. Xavier, Naizhong Hu, Qian Cao, Yufang Wang, Yinglei Miao, Hongjie Zhang, Xiaoping Lv, Xiang Gao, Hu Zhang, Jingling Su, Bai‐Sui Feng, Ye Zhao, Liangru Zhu, Yan Chen, Lanxiang Zhu, Chunxiao Chen, Yali Wang, Ying-De Wang, Zhi Pang, Yingxuan Chen, Xiaolan Zhang, Hui Li, Yu Qin, Mei Ye, Sumin Zhang, Wen Tang, Mei Wang, Xiaocang Cao, Ruixin Zhu, Guangxi Zhou, Zhaolian Bian, Xiao‐Feng Guo, Xiaoli Wu, Jinchun Liu, Wei Xu, Yuqin Li, Qin Guo, Zhiguo Guo, Shu Zhu, Dalin Li, Jianjun Liu, Tian Ge, Judy H. Cho, Mark J. Daly, Dermot McGovern, Byong Duk Ye, Kyuyoung Song, Yoichi Kakuta, Mingsong Li, Hailiang Huang,

Digestive system and related health

Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract with the following two subtypes: Crohn’s disease (CD) and ulcerative colitis (UC). To date, most IBD genetic associations were derived from individuals of European (EUR) ancestries. Here we report the largest IBD study of individuals of East Asian (EAS) ancestries, including 14,393 cases and 15,456 controls. We found 80 IBD loci in EAS alone and 320 when meta-analyzed with ~370,000 EUR individuals (~30,000 cases), among which 81 are new. EAS-enriched coding variants implicate many new IBD genes, including ADAP1 and GIT2. Although IBD genetic effects are generally consistent across ancestries, genetics underlying CD appears more ancestry dependent than UC, driven by allele frequency (NOD2) and effect (TNFSF15). We extended the IBD polygenic risk score (PRS) by incorporating both ancestries, greatly improving its accuracy and highlighting the importance of diversity for the equitable deployment of PRS. Genome-wide association analyses across individuals of East Asian and European ancestries identify new risk loci for inflammatory bowel diseases. A polygenic risk score derived from the combined datasets shows improved prediction accuracy.