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

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收录情况: ◇ SCIE ◇ 自然指数

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单位: [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 [51]Imperial Coll London, London, England [52]Addenborookes Hosp, Cambridge, England [53]Univ Chicago, Chicago, IL USA [54]Univ Maribor, Ctr Human Mol Genet & Pharmacogen, Fac Med, Maribor, Slovenia [55]QIMR Berghofer MRI, Herston, Qld, Australia [56]Montreal Heart Inst Ctr, Montreal, PQ, Canada [57]Univ Hosp Zurich, Dept Gastroenterol & Hepatol, Zurich, Switzerland [58]Icahn Sch Med Mt Sinai, Dr Henry D Janowitz Div Gastroenterol, New York, NY 10029 USA [59]Mt Sinai Hosp, Toronto, ON, Canada [60]St Antoine Hosp, AP HP, Paris, France [61]Univ Hosp Leuven, Dept Gastroenterol, Leuven, Belgium [62]Univ Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands [63]Univ Med Ctr Groningen, Groningen, Netherlands [64]Broad Inst MIT & Harvard, Cambridge, MA 02142 USA [65]Anhui Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Hefei, Peoples R China [66]Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Gastroenterol, Hangzhou, Peoples R China [67]Sichuan Univ, West China Hosp, Dept Gastroenterol, Chengdu, Peoples R China [68]Kunming Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Kunming, Yunnan, Peoples R China [69]Nanjing Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Nanjing, Peoples R China [70]Guangxi Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Nanning, Peoples R China [71]Sun Yat Sen Univ, Affiliated Hosp 6, Dept Gastroenterol, Guangzhou, Peoples R China [72]Xiamen Univ, Zhongshan Hosp, Dept Gastroenterol, Xiamen, Peoples R China [73]Zhengzhou Univ, Affiliated Hosp 2, Dept Gastroenterol, Zhengzhou, Peoples R China [74]Zhengzhou Univ, Affiliated Hosp 1, Dept Gastroenterol, Zhengzhou, Peoples R China [75]Huazhong Univ Sci & Technol, Union Hosp, Dept Gastroenterol, Wuhan, Peoples R China [76]Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Gastroenterol, Hangzhou, Peoples R China [77]Soochow Univ, Affiliated Hosp 1, Dept Gastroenterol, Suzhou, Peoples R China [78]Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Gastroenterol, Hangzhou, Peoples R China [79]Datong Third Peoples Hosp, Dept Gastroenterol, Datong, Peoples R China [80]Dalian Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Dalian, Peoples R China [81]Nanjing Med Univ, Affiliated Suzhou Hosp, Dept Gastroenterol, Suzhou, Peoples R China [82]Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Gastroenterol & Hepatol, Shanghai, Peoples R China [83]Hebei Med Univ, Hosp 2, East Branch, Dept Gastroenterol, Shijiazhuang, Hebei, Peoples R China [84]Harbin Med Univ, Hosp 2, Dept Gastroenterol, Harbin, Peoples R China [85]Huazhong Univ Sci & Technol, Tongji Hosp, Dept Gastroenterol, Wuhan, Peoples R China [86]Wuhan Univ, Zhongnan Hosp, Dept Gastroenterol, Wuhan, Peoples R China [87]Nanjing Univ Chinese Med, TCM Affiliated, Nanjing Hosp, Dept Colorectal Surg, Nanjing, Peoples R China [88]Soochow Univ, Hosp 2, Dept Gastroenterol, Suzhou, Peoples R China [89]Yangzhou Univ, Affiliated Hosp, Dept Gastroenterol, Yangzhou, Jiangsu, Peoples R China [90]Tianjin Med Univ, Gen Hosp, Dept Gastroenterol, Tianjin, Peoples R China [91]Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai, Peoples R China [92]Jining Med Univ, Affiliated Hosp, Dept Gastroenterol, Jining, Peoples R China [93]Nantong Univ, Nantong Peoples Hosp 3, Dept Gastroenterol, Nantong, Peoples R China [94]Shanxi Prov Peoples Hosp, Dept Gastroenterol, Taiyuan, Peoples R China [95]Wenzhou Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Wenzhou, Peoples R China [96]Shanxi Med Univ, Hosp 1, Dept Gastroenterol, Taiyuan, Peoples R China [97]Nanjing Med Univ, Affiliated Changzhou Peoples Hosp 2, Dept Colorectal Surg, Changzhou, Jiangsu, Peoples R China [98]Jilin Univ, Bethune Affiliated Hosp 1, Dept Gastroenterol, Changchun, Peoples R China [99]Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, Changsha, Peoples R China [100]Anhui Med Univ, Suzhou Hosp, Dept Gastroenterol, Suzhou, Peoples R China
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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.

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大类 | 1 区 生物学
小类 | 1 区 遗传学
最新[2025]版:
大类 | 1 区 生物学
小类 | 1 区 遗传学
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出版当年[2021]版:
Q1 GENETICS & HEREDITY
最新[2023]版:
Q1 GENETICS & HEREDITY

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第一作者:
第一作者单位: [1]Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Ctr IBD Res,Dept Gastroenterol, Shanghai, Peoples R China [9]Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Fukuoka, Japan
通讯作者:
通讯机构: [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 [9]Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Fukuoka, Japan [25]Harvard Med Sch, Dept Med, Boston, MA 02115 USA
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