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

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Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries
Nature Genetics ( IF 30.8 ) Pub Date : 2023-05-08 , DOI: 10.1038/s41588-023-01384-0
Zhanju Liu ₁ , Ruize Liu _{2,

3} , Han Gao ₁ , Seulgi Jung ₄ , Xiang Gao ₁ , Ruicong Sun ₁ , Xiaoming Liu ₅ , Yongjae Kim ₄ , Ho-Su Lee ₄ , Yosuke Kawai ₆ , Masao Nagasaki _{7,

8} , Junji Umeno ₉ , Katsushi Tokunaga ₆ , Yoshitaka Kinouchi ₁₀ , Atsushi Masamune ₁₁ , Wenzhao Shi ₁₂ , Chengguo Shen ₁₂ , Zhenglin Guo ₃ , Kai Yuan _{2,

3} , , , , Shu Zhu ₁₃ , Dalin Li ₁₄ , Jianjun Liu _{15,

16} , Tian Ge _{17,

18,

19} , Judy Cho ₂₀ , Mark J Daly _{2,

21,

22} , Dermot P B McGovern ₁₄ , Byong Duk Ye ₂₃ , Kyuyoung Song ₄ , Yoichi Kakuta ₁₁ , Mingsong Li ₅ , Hailiang Huang _{2,

3,

24}

Affiliation

Center for IBD Research, Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
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.
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Inflammatory Bowel Diseases Research Center, Department of Gastroenterology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Genome Medical Science Project, National Center for Global Health and Medicine, Tokyo, Japan.
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.
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Student Healthcare Center, Institute for Excellence in Higher Education, Tohoku University, Sendai, Japan.
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Digital Health China Technologies Corp Ltd., Beijing, China.
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.
Widjaja Inflammatory Bowel Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Genome Institute of Singapore, Singapore, Singapore.
Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
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.
Icahn School of Medicine at Mount Sinai, New York, NY, 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.
Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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 ~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.

中文翻译：

东亚和欧洲祖先炎症性肠病的遗传结构

炎症性肠病（IBD）是胃肠道的慢性疾病，具有以下两种亚型：克罗恩病（CD）和溃疡性结肠炎（UC）。迄今为止，大多数 IBD 遗传关联都源自欧洲 (EUR) 血统的个体。在此，我们报告了针对东亚 (EAS) 血统个体的最大规模 IBD 研究，包括 14,393 例病例和 15,456 例对照。我们仅在 EAS 中就发现了 80 个 IBD 位点，对约 370,000 欧元个体（约 30,000 例）进行荟萃分析时发现了 320 个 IBD 位点，其中 81 个是新的。富含 EAS 的编码变体涉及许多新的 IBD 基因，包括ADAP1和GIT2。尽管 IBD 遗传效应在不同祖先中通常是一致的，但 CD 的遗传学似乎比 UC 更依赖于祖先，这是由等位基因频率 ( NOD2 ) 和效应 ( TNFSF15 ) 驱动的。我们通过合并两个血统扩展了 IBD 多基因风险评分 (PRS)，大大提高了其准确性，并强调了多样性对于 PRS 公平部署的重要性。

更新日期：2023-05-09

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