TY - JOUR
T1 - Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries
AU - Chinese Inflammatory Bowel Disease Genetics Consortium
AU - FinnGen
AU - International Inflammatory Bowel Disease Genetics Consortium
AU - Liu, Zhanju
AU - Liu, Ruize
AU - Gao, Han
AU - Jung, Seulgi
AU - Gao, Xiang
AU - Sun, Ruicong
AU - Liu, Xiaoming
AU - Kim, Yongjae
AU - Lee, Ho Su
AU - Kawai, Yosuke
AU - Nagasaki, Masao
AU - Umeno, Junji
AU - Tokunaga, Katsushi
AU - Kinouchi, Yoshitaka
AU - Masamune, Atsushi
AU - Shi, Wenzhao
AU - Shen, Chengguo
AU - Guo, Zhenglin
AU - Yuan, Kai
AU - Abreu, Maria
AU - Achkar, Jean Paul
AU - Andersen, Vibeke
AU - Bernstein, Charles
AU - Brant, Steven R.
AU - Bujanda, Luis
AU - Ng, Siew Chien
AU - Denson, Lee A.
AU - Duerr, Richard H.
AU - Ferguson, Lynnette R.
AU - Franchimont, Denis
AU - Franke, Andre
AU - Gearry, Richard
AU - Hakonarson, Hakon
AU - Halfvarson, Jonas
AU - Heller, Caren
AU - Julià, Antonio
AU - Kelsen, Judith
AU - Khalili, Hamed
AU - Kugathasan, Subramaniam
AU - Kupcinskas, Juozas
AU - Latiano, Anna
AU - Louis, Edouard
AU - Malekzadeh, Reza
AU - McCauley, Jacob L.
AU - Moran, Christopher
AU - Okou, David
AU - Weersma, Rinse K.
AU - Gao, Xiang
AU - Li, Hui
AU - Xu, Wei
N1 - Funding Information:
W.S. and C.S. are employees of Digital Health China Technologies Corp. Ltd. M.J.D. is a founder of Maze Therapeutics. D.P.B.M. has received consultancy fees from Prometheus Biosciences, Prometheus Laboratories, Takeda, Gilead, Pfizer. Stock—Prometheus Biosciences. B.D.Y. has served on advisory boards for AbbVie Korea, Celltrion, Daewoong Pharma, Ferring Korea, Janssen Korea, Pfizer Korea and Takeda Korea; has received research grants from Celltrion and Pfizer Korea; has received consulting fees from Chong Kun Dang Pharm., CJ Red BIO, Cornerstones Health, Daewoong Pharma, IQVIA, Kangstem Biotech, Korea United Pharm. Inc., Medtronic Korea, NanoEntek and Takeda; and has received speaking fees from AbbVie Korea, Celltrion, Ferring Korea, IQVIA, Janssen Korea, Pfizer Korea, Takeda and Takeda Korea. H.H. received consultancy fees from Ono Pharmaceutical and an honorarium from Xian Janssen Pharmaceutical. The remaining authors declare no competing interests.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2023/5/8
Y1 - 2023/5/8
N2 - 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.
AB - 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.
U2 - 10.1038/s41588-023-01384-0
DO - 10.1038/s41588-023-01384-0
M3 - Article
C2 - 37156999
AN - SCOPUS:85158880855
SN - 1061-4036
VL - 55
SP - 796
EP - 806
JO - Nature genetics
JF - Nature genetics
IS - 5
ER -