机构：[1]Center for IBD Research, Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China[2]Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA[3]Stanley Center for PsychiatricResearch, The Broad Institute of MIT and Harvard, Cambridge, MA, USA[4]Department of Biochemistry and Molecular Biology, University of Ulsan Collegeof Medicine, Seoul, Korea[5]Inflammatory Bowel Diseases Research Center, Department of Gastroenterology, The Third Affiliated Hospital of GuangzhouMedical University, Guangzhou, China[6]Genome Medical Science Project, National Center for Global Health and Medicine, Tokyo, Japan[7]HumanBiosciences Unit for the Top Global Course Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan[8]Centerfor Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan[9]Department of Medicine and Clinical Science, Graduate Schoolof Medical Sciences, Kyushu University, Fukuoka, Japan[10]Student Healthcare Center, Institute for Excellence in Higher Education, Tohoku University,Sendai, Japan[11]Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan[12]Digital Health China Technologies Corp Ltd.,Beijing, China[13]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[14]Widjaja Inflammatory Bowel Research Institute,Cedars-Sinai Medical Center, Los Angeles, CA, USA[15]Genome Institute of Singapore, Singapore, Singapore[16]Yong Loo Lin School of Medicine, NationalUniversity of Singapore, Singapore, Singapore[17]Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA,USA[18]Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA[19]Centerfor Precision Psychiatry, Massachusetts General Hospital, Boston, MA, USA[20]Icahn School of Medicine at Mount Sinai, New York, NY, USA[21]Institutefor Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland[22]Program in Medical andPopulation Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA[23]Department of Gastroenterology and Inflammatory Bowel DiseaseCenter, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea[24]Department of Medicine, Harvard Medical School, Boston, MA,USA
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.
基金：
National Natural Science Foundation of China; NIDDK; Stanley Center for Psychiatric Research; JSPS KAKENHI; Japan Agency for Medical Research and Development (AMED); Labour Sciences Research Grants for Research on Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan; National Research Foundation of Korea; Business Finland; AbbVie Inc; AstraZeneca UK Ltd; Biogen MA Inc; Bristol Myers Squibb (and Celgene Corporation & Celgene International II Sarl); Genentech Inc [91942312, 81630017, K01DK114379, R01DK129364]; Merck Sharp Dohme Corp [81870389, 82070565, JP19km0405501, JP19km0405205, 2017R1A2A1A05001119]; Pfizer Inc; GlaxoSmithKline Intellectual Property Development Ltd [U24DK062429, U01DK062422]; Sanofi US Services Inc [U01DK062413, 21K07884, 2020R1A2C2003275]; Maze Therapeutics Inc; Janssen Biotech Inc [21K07955, JP18kk0305002]; Novartis AG and Boehringer Ingelheim [HUS 4685/31/2016]; [UH 4386/31/2016]
第一作者机构：[1]Center for IBD Research, Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
通讯作者：
通讯机构：[1]Center for IBD Research, Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China[2]Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA[3]Stanley Center for PsychiatricResearch, The Broad Institute of MIT and Harvard, Cambridge, MA, USA[24]Department of Medicine, Harvard Medical School, Boston, MA,USA
推荐引用方式(GB/T 7714)：
Zhanju Liu,Ruize Liu,Han Gao,et al.Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries[J].NATURE GENETICS.2023,55(5):796-+.doi:10.1038/s41588-023-01384-0.
APA：
Zhanju Liu,Ruize Liu,Han Gao,Seulgi Jung,Xiang Gao...&Chinese Inflammatory Bowel Disease Genetics Consortium.(2023).Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries.NATURE GENETICS,55,(5)
MLA：
Zhanju Liu,et al."Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries".NATURE GENETICS 55..5(2023):796-+
生物学