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

被引：100

作者：

Liu, Zhanju ^{[1
,9
]}

Liu, Ruize ^{[2
,3
]}

Gao, Han ^{[1
]}

Jung, Seulgi ^{[4
]}

Gao, Xiang ^{[1
,71
]}

Sun, Ruicong ^{[1
]}

Liu, Xiaoming ^{[5
]}

Kim, Yongjae ^{[4
]}

Lee, Ho-Su ^{[4
]}

Kawai, Yosuke ^{[6
]}

Nagasaki, Masao ^{[7
,8
]}

Umeno, Junji ^{[9
]}

Tokunaga, Katsushi ^{[6
]}

Kinouchi, Yoshitaka ^{[10
]}

Masamune, Atsushi ^{[11
]}

Shi, Wenzhao ^{[12
]}

Shen, Chengguo ^{[12
]}

Guo, Zhenglin ^{[3
]}

Yuan, Kai ^{[2
,3
]}

Zhu, Shu ^{[13
]}

Li, Dalin ^{[14
]}

Liu, Jianjun ^{[15
,16
]}

Ge, Tian ^{[17
,18
,19
]}

Cho, Judy ^{[20
]}

Daly, Mark J. ^{[2
,21
,22
,23
,24
]}

McGovern, Dermot P. B. ^{[14
]}

Ye, Byong Duk ^{[23
,24
]}

Song, Kyuyoung ^{[4
]}

Kakuta, Yoichi ^{[11
]}

Li, Mingsong ^{[5
]}

Huang, Hailiang ^{[2
,3
,25
]}

Abreu, Maria ^{[26
]}

Achkar, Jean-Paul ^{[27
]}

Andersen, Vibeke ^{[28
]}

Bernstein, Charles ^{[29
]}

Brant, Steven R. ^{[30
]}

Bujanda, Luis ^{[31
]}

Ng, Siew Chien ^{[32
]}

Cho, Judy ^{[20
]}

Daly, Mark J. ^{[2
,21
,22
,23
,24
]}

Denson, Lee A. ^{[33
]}

Duerr, Richard H. ^{[34
]}

Ferguson, Lynnette R. ^{[35
]}

Franchimont, Denis ^{[36
]}

Franke, Andre ^{[37
]}

Gearry, Richard ^{[38
]}

Hakonarson, Hakon ^{[39
]}

Halfvarson, Jonas ^{[40
]}

Heller, Caren ^{[41
]}

Huang, Hailiang ^{[2
,3
,25
]}

机构：

[1] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Ctr IBD Res,Dept Gastroenterol, Shanghai, Peoples R China

[2] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[3] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA

[4] Univ Ulsan, Coll Med, Dept Biochem & Mol Biol, Seoul, South Korea

[5] Guangzhou Med Univ, Affiliated Hosp 3, Dept Gastroenterol, Inflammatory Bowel Dis Res Ctr, Guangzhou, Peoples R China

[6] Natl Ctr Global Hlth & Med, Genome Med Sci Project, Tokyo, Japan

[7] Kyoto Univ, Human Biosci Unit Top Global Course Ctr Promot In, Kyoto, Japan

[8] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan

[9] Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Fukuoka, Japan

[10] Tohoku Univ, Inst Excellence Higher Educ, Student Healthcare Ctr, Sendai, Miyagi, Japan

[11] Tohoku Univ, Grad Sch Med, Div Gastroenterol, Sendai, Miyagi, Japan

[12] Digital Hlth China Technol Corp Ltd, Beijing, Peoples R China

[13] Univ Sci & Technol China, Div Life Sci & Med, CAS Key Lab Innate Immun & Chron Dis, Inst Immunol,Sch Basic Med Sci, Hefei, Peoples R China

[14] Cedars Sinai Med Ctr, Widjaja Inflammatory Bowel Res Inst, Los Angeles, CA 90048 USA

[15] Genome Inst Singapore, Singapore, Singapore

[16] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore, Singapore

[17] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA

[18] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Genom Med, Boston, MA 02114 USA

[19] Massachusetts Gen Hosp, Ctr Precis Psychiat, Boston, MA 02114 USA

[20] Icahn Sch Med Mt Sinai, New York, NY 10029 USA

[21] Univ Helsinki, Helsinki Inst Life Sci HiLIFE, Inst Mol Med Finland FIMM, Helsinki, Finland

[22] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA

[23] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Gastroenterol, Seoul, South Korea

[24] Univ Ulsan, Coll Med, Asan Med Ctr, Inflammatory Bowel Dis Ctr, Seoul, South Korea

[25] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[26] Univ Miami, Dept Med, Leonard M Miller Sch Med, Div Gastroenterol, Miami, FL USA

[27] Cleveland Clin, Cleveland, OH 44106 USA

[28] Hosp Southern Jutland, Focused Res Unit Mol Diagnost & Clin Res, Aabenraa, Denmark

[29] Univ Manitoba, IBD Clin & Res Ctr, Winnipeg, MB, Canada

[30] Rutgers State Univ, New Brunswick, NJ USA

[31] Osakidetza Basque Hlth Serv, Bilbao, Spain

[32] Chinese Univ Hong Kong, Hong Kong, Peoples R China

[33] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA

[34] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA

[35] Univ Auckland, Auckland, New Zealand

[36] Free Univ Brussels, Erasme Hosp, Dept Gastroenterol, Brussels, Belgium

[37] Christian Albrechts Univ Kiel, Inst Clin Mol Biol IKMB, Kiel, Germany

[38] Univ Otago, Dept Med, Christchurch, New Zealand

[39] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[40] Orebro Univ, Fac Med & Hlth, Dept Gastroenterol, Orebro, Sweden

[41] Crohns & Colitis Fdn, New York, NY USA

[42] Vall dHebron Univ Hosp, Rheumatol Res Grp, Barcelona, Spain

[43] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA

[44] Emory Univ, Atlanta, GA 30322 USA

[45] Lithuanian Univ Hlth Sci, Dept Gastroenterol, Kaunas, Lithuania

[46] Fdn IRCCS Casa Sollievo Sofferenza, Gastroenterol Unit, Foggia, Italy

[47] Univ Liege, ULG, Liege, Belgium

[48] Univ Tehran Med Sci, DDRI, Tehran, Iran

[49] Univ Miami, John P Hussman Inst Human Genom, Leonard M Miller Sch Med, Miami, FL USA

[50] MassGen Hosp Children, Boston, MA USA

来源：

NATURE GENETICS | 2023年 / 55卷 / 05期

基金：

中国国家自然科学基金; 新加坡国家研究基金会;

关键词：

GENOME-WIDE ASSOCIATION; ADDITIONAL SUSCEPTIBILITY LOCI; ULCERATIVE-COLITIS; CROHNS-DISEASE; IMMUNOCHIP ANALYSIS; TGF-BETA; IDENTIFICATION; VARIANTS; KOREANS; RISK;

D O I：

10.1038/s41588-023-01384-0

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 similar to 370,000 EUR individuals (similar to 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.

引用

页码：796 / +

页数：30

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