Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries.
Authors
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, 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
Year of publication
2023Journal
NAT GENETVolume
55Issue
5Abstract
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.