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

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

Nature Genetics

10.1038/s41588-023-01384-0

https://doi.org/10.1038/s41588-023-01384-0

Zhanju Liu, Ruize Liu, Han Gao, Seulgi Jung, Xiang Gao, Ruicong Sun, Xiaoming Liu, Yongjae Kim, Ho-Su Lee, Yosuke Kawai, Masao Nagasaki, Junji Umeno, Katsushi Tokunaga, Yoshitaka Kinouchi, Atsushi Masamune, Wenzhao Shi, Chengguo Shen, Zhenglin Guo, Kai Yuan, , , Maria Abreu, Jean-Paul Achkar, Vibeke Andersen, Charles Bernstein, Steven R. Brant, Luis Bujanda, Siew Chien Ng, Lee A. Denson, Richard H. Duerr, Lynnette R. Ferguson, Denis Franchimont, Andre Franke, Richard Gearry, Hakon Hakonarson, Jonas Halfvarson, Caren Heller, Antonio Julià, Judith Kelsen, Hamed Khalili, Subramaniam Kugathasan, Juozas Kupcinskas, Anna Latiano, Edouard Louis, Reza Malekzadeh, Jacob L. McCauley, Christopher Moran, David Okou, Tim Orchard, Aarno Palotie, Miles Parkes, Joel Pekow, Uroš Potočnik, Graham Radford-Smith, John D. Rioux, Gerhard Rogler, Bruce Sands, Mark 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, Baisui Feng, Ye Zhao, Liangru Zhu, Yan Chen, Lanxiang Zhu, Chunxiao Chen, Yali Wang, Yingde Wang, Zhi Pang, Yingxuan Chen, Xiaolan Zhang, Hui Li, Qin Yu, Mei Ye, Sumin Zhang, Wen Tang, Mei Wang, Xiaocang Cao, Ruixin Zhu, Guangxi Zhou, Zhaolian Bian, Xiaofeng Guo, Xiaoli Wu, Jinchun Liu, Wei Xu, Yuqin Li, Qin Guo, Zhiguo Guo, Shu Zhu, Dalin Li, Jianjun Liu, Tian Ge, Judy Cho, Mark J. Daly, Dermot P. B. McGovern, Byong Duk Ye, Kyuyoung Song, Yoichi Kakuta, Mingsong Li, Hailiang Huang

08 May 2023

Liu, Z., Liu, R., Gao, H., Jung, S., Gao, X., Sun, R., Liu, X., Kim, Y., Lee, H.-S., Kawai, Y., Nagasaki, M., Umeno, J., Tokunaga, K., Kinouchi, Y., Masamune, A., Shi, W., Shen, C., Guo, Z., Yuan, K., … Huang, H. (2023). Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries. Nature Genetics, 55(5), 796–806. https://doi.org/10.1038/s41588-023-01384-0

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.

Publisher Copyright

There was no specific funding for the research done

This is a post-peer-review, pre-copyedit version of an article published in Nature Genetics. The final authenticated version is available online at: http://dx.doi.org/10.1038/s41588-023-01384-0

https://oar.a-star.edu.sg/communities-collections/articles/22591

1061-4036
1546-1718

Genome Institute of Singapore

https://doi.org/10.1038/s41588-023-01384-0