Article (Scientific journals)
Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries.
Liu, Zhanju; Liu, Ruize; Gao, Han et al.
2023In Nature Genetics, 55 (5), p. 796-806
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Keywords :
ADAP1 protein, human; GIT2 protein, human; NOD2 protein, human; TNFSF15 protein, human; Tumor Necrosis Factor Ligand Superfamily Member 15; Humans; Colitis, Ulcerative/genetics; Crohn Disease/genetics; East Asian People; European People; Genetic Predisposition to Disease; Genome-Wide Association Study; Inflammatory Bowel Diseases/genetics; Polymorphism, Single Nucleotide/genetics; Tumor Necrosis Factor Ligand Superfamily Member 15/genetics
Abstract :
[en] 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.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Liu, Zhanju ;  Center for IBD Research, Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. zhanjuliu@tongji.edu.cn.
Liu, Ruize;  Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. ; Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Gao, Han;  Center for IBD Research, Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Jung, Seulgi ;  Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Gao, Xiang;  Center for IBD Research, Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Sun, Ruicong;  Center for IBD Research, Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Liu, Xiaoming;  Inflammatory Bowel Diseases Research Center, Department of Gastroenterology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Kim, Yongjae;  Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Lee, Ho-Su;  Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Kawai, Yosuke ;  Genome Medical Science Project, National Center for Global Health and Medicine, Tokyo, Japan.
Nagasaki, Masao ;  Human Biosciences Unit for the Top Global Course Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan. ; Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Umeno, Junji ;  Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Tokunaga, Katsushi ;  Genome Medical Science Project, National Center for Global Health and Medicine, Tokyo, Japan.
Kinouchi, Yoshitaka;  Student Healthcare Center, Institute for Excellence in Higher Education, Tohoku University, Sendai, Japan.
Masamune, Atsushi ;  Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Shi, Wenzhao;  Digital Health China Technologies Corp Ltd., Beijing, China.
Shen, Chengguo;  Digital Health China Technologies Corp Ltd., Beijing, China.
Guo, Zhenglin;  Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yuan, Kai ;  Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. ; Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FinnGen
International Inflammatory Bowel Disease Genetics, Consortium
Chinese Inflammatory Bowel Disease Genetics, Consortium
Zhu, Shu ;  Institute of Immunology, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Li, Dalin ;  Widjaja Inflammatory Bowel Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Liu, Jianjun ;  Genome Institute of Singapore, Singapore, Singapore. ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Ge, Tian;  Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. ; Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. ; Center for Precision Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
Cho, Judy ;  Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Daly, Mark J;  Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. ; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland. ; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
McGovern, Dermot P B;  Widjaja Inflammatory Bowel Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Ye, Byong Duk ;  Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Song, Kyuyoung ;  Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea. kysong@amc.seoul.kr.
Kakuta, Yoichi ;  Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. ykakuta@med.tohoku.ac.jp.
Li, Mingsong ;  Inflammatory Bowel Diseases Research Center, Department of Gastroenterology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. lims661216@163.com.
Huang, Hailiang ;  Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. hhuang@broadinstitute.org. ; Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA. hhuang@broadinstitute.org. ; Department of Medicine, Harvard Medical School, Boston, MA, USA. hhuang@broadinstitute.org.
More authors (24 more) Less
Other collaborator :
Abreu, Maria
Achkar, Jean-Paul
Andersen, Vibeke
Bernstein, Charles
Brant, Steven R
Bujanda, Luis
Ng, Siew Chien
Denson, Lee A
Duerr, Richard H
Ferguson, Lynnette R
Franchimont, Denis
Franke, Andre
Gearry, Richard
Hakonarson, Hakon
Halfvarson, Jonas
Heller, Caren
Julià, Antonio
Kelsen, Judith
Khalili, Hamed
Kugathasan, Subramaniam
Kupcinskas, Juozas
Latiano, Anna
Louis, Edouard  ;  Centre Hospitalier Universitaire de Liège - CHU > > Service de gastroentérologie, hépatologie, onco. digestive
Malekzadeh, Reza
McCauley, Jacob L
Moran, Christopher
Okou, David
Orchard, Tim
Palotie, Aarno
Parkes, Miles
Pekow, Joel
Potočnik, Uroš
Radford-Smith, Graham
Rioux, John D
Rogler, Gerhard
Sands, Bruce
Silverberg, Mark
Sokol, Harry
Vermeire, Séverine
Weersma, Rinse K
Xavier, Ramnik J
Hu, Naizhong
Cao, Qian
Wang, Yufang
Miao, Yinglei
Zhang, Hongjie
Lv, Xiaoping
Gao, Xiang
Zhang, Hu
Su, Jingling
Feng, Baisui
Zhao, Ye
Zhu, Liangru
Chen, Yan
Zhu, Lanxiang
Chen, Chunxiao
Wang, Yali
Wang, Yingde
Pang, Zhi
Chen, Yingxuan
Zhang, Xiaolan
Li, Hui
Yu, Qin
Ye, Mei
Zhang, Sumin
Tang, Wen
Wang, Mei
Cao, Xiaocang
Zhu, Ruixin
Zhou, Guangxi
Bian, Zhaolian
Guo, Xiaofeng
Wu, Xiaoli
Liu, Jinchun
Xu, Wei
Li, Yuqin
Guo, Qin
Guo, Zhiguo
More authors (68 more) Less
Language :
English
Title :
Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries.
Publication date :
May 2023
Journal title :
Nature Genetics
ISSN :
1061-4036
eISSN :
1546-1718
Publisher :
Nature Publishing Group, Gb
Volume :
55
Issue :
5
Pages :
796-806
Peer reviewed :
Peer Reviewed verified by ORBi
Funding number :
R56 HG012354/HG/NHGRI NIH HHS/United States; U01 DK062413/DK/NIDDK NIH HHS/United States; R01 DK129364/DK/NIDDK NIH HHS/United States; K01 DK114379/DK/NIDDK NIH HHS/United States; R01 HG012354/HG/NHGRI NIH HHS/United States
Commentary :
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
Available on ORBi :
since 17 December 2023

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