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Identification of type 2 diabetes loci in 433,540 East Asian individuals

Author

Listed:
  • Cassandra N. Spracklen

    (University of North Carolina at Chapel Hill
    University of Massachusetts)

  • Momoko Horikoshi

    (RIKEN Centre for Integrative Medical Sciences)

  • Young Jin Kim

    (National Institute of Health)

  • Kuang Lin

    (University of Oxford)

  • Fiona Bragg

    (University of Oxford)

  • Sanghoon Moon

    (National Institute of Health)

  • Ken Suzuki

    (RIKEN Centre for Integrative Medical Sciences
    RIKEN Centre for Integrative Medical Sciences
    The University of Tokyo
    Osaka University Graduate School of Medicine)

  • Claudia H. T. Tam

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Yasuharu Tabara

    (Kyoto University Graduate School of Medicine)

  • Soo-Heon Kwak

    (Seoul National University Hospital)

  • Fumihiko Takeuchi

    (National Center for Global Health and Medicine)

  • Jirong Long

    (Vanderbilt University Medical Center)

  • Victor J. Y. Lim

    (National University of Singapore and National University Health System)

  • Jin-Fang Chai

    (National University of Singapore and National University Health System)

  • Chien-Hsiun Chen

    (Academia Sinica)

  • Masahiro Nakatochi

    (Nagoya University Graduate School of Medicine)

  • Jie Yao

    (The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
    Harbor-UCLA Medical Center)

  • Hyeok Sun Choi

    (Hallym University)

  • Apoorva K. Iyengar

    (University of North Carolina at Chapel Hill)

  • Hannah J. Perrin

    (University of North Carolina at Chapel Hill)

  • Sarah M. Brotman

    (University of North Carolina at Chapel Hill)

  • Martijn van de Bunt

    (University of Oxford
    University of Oxford)

  • Anna L. Gloyn

    (University of Oxford
    University of Oxford
    Oxford University Hospitals NHS Foundation Trust, Churchill Hospital
    Stanford University)

  • Jennifer E. Below

    (Vanderbilt University Medical Center
    The University of Texas Health Science Center at Houston)

  • Michael Boehnke

    (University of Michigan)

  • Donald W. Bowden

    (Wake Forest School of Medicine
    Wake Forest School of Medicine)

  • John C. Chambers

    (Nanyang Technological University
    Imperial College London
    London North West Healthcare NHS Trust
    Imperial College London)

  • Anubha Mahajan

    (University of Oxford
    University of Oxford
    Genentech)

  • Mark I. McCarthy

    (University of Oxford
    University of Oxford
    Oxford University Hospitals NHS Foundation Trust, Churchill Hospital
    Genentech)

  • Maggie C. Y. Ng

    (Vanderbilt University Medical Center
    Wake Forest School of Medicine)

  • Lauren E. Petty

    (Vanderbilt University Medical Center
    The University of Texas Health Science Center at Houston)

  • Weihua Zhang

    (Imperial College London
    London North West Healthcare NHS Trust)

  • Andrew P. Morris

    (University of Oxford
    University of Liverpool
    University of Manchester)

  • Linda S. Adair

    (University of North Carolina at Chapel Hill)

  • Masato Akiyama

    (RIKEN Centre for Integrative Medical Sciences
    RIKEN Centre for Integrative Medical Sciences
    Kyushu University)

  • Zheng Bian

    (Chinese Academy of Medical Sciences)

  • Juliana C. N. Chan

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong
    The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Li-Ching Chang

    (Academia Sinica)

  • Miao-Li Chee

    (Singapore National Eye Centre)

  • Yii-Der Ida Chen

    (The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
    Harbor-UCLA Medical Center)

  • Yuan-Tsong Chen

    (Academia Sinica)

  • Zhengming Chen

    (University of Oxford)

  • Lee-Ming Chuang

    (National Taiwan University Hospital
    National Taiwan University)

  • Shufa Du

    (University of North Carolina at Chapel Hill)

  • Penny Gordon-Larsen

    (University of North Carolina at Chapel Hill)

  • Myron Gross

    (University of Minnesota)

  • Xiuqing Guo

    (The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
    Harbor-UCLA Medical Center)

  • Yu Guo

    (Chinese Academy of Medical Sciences)

  • Sohee Han

    (National Institute of Health)

  • Annie-Green Howard

    (University of North Carolina at Chapel Hill)

  • Wei Huang

    (Chinese National Human Genome Center at Shanghai)

  • Yi-Jen Hung

    (Tri-Service General Hospital Songshan Branch
    National Defense Medical Center)

  • Mi Yeong Hwang

    (National Institute of Health)

  • Chii-Min Hwu

    (Taipei Veterans General Hospital
    National Yang-Ming University)

  • Sahoko Ichihara

    (Jichi Medical University School of Medicine)

  • Masato Isono

    (National Center for Global Health and Medicine)

  • Hye-Mi Jang

    (National Institute of Health)

  • Guozhi Jiang

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Jost B. Jonas

    (Medical Faculty Mannheim of the University of Heidelberg)

  • Yoichiro Kamatani

    (RIKEN Centre for Integrative Medical Sciences
    The University of Tokyo)

  • Tomohiro Katsuya

    (Osaka University Graduate School of Medicine
    Osaka University)

  • Takahisa Kawaguchi

    (Kyoto University Graduate School of Medicine)

  • Chiea-Chuen Khor

    (Singapore National Eye Centre
    Technology and Research
    University of the Ryukyus)

  • Katsuhiko Kohara

    (Ehime University Faculty of Collaborative Regional Innovation)

  • Myung-Shik Lee

    (Yonsei University College of Medicine
    Sungkyunkwan University School of Medicine)

  • Nanette R. Lee

    (University of San Carlos)

  • Liming Li

    (Peking University)

  • Jianjun Liu

    (Technology and Research
    National University of Singapore and National University Health System)

  • Andrea O. Luk

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Jun Lv

    (Peking University)

  • Yukinori Okada

    (Osaka University Graduate School of Medicine
    Osaka University)

  • Mark A. Pereira

    (University of Minnesota)

  • Charumathi Sabanayagam

    (Singapore National Eye Centre
    Duke-NUS Medical School
    National University of Singapore and National University Health System)

  • Jinxiu Shi

    (University of Minnesota)

  • Dong Mun Shin

    (National Institute of Health)

  • Wing Yee So

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Atsushi Takahashi

    (RIKEN Centre for Integrative Medical Sciences
    National Cerebral and Cardiovascular Center)

  • Brian Tomlinson

    (The Chinese University of Hong Kong
    Macau University of Science and Technology)

  • Fuu-Jen Tsai

    (China Medical University Hospital)

  • Rob M. van Dam

    (National University of Singapore and National University Health System
    National University of Singapore and National University Health System)

  • Yong-Bing Xiang

    (Shanghai Jiaotong University School of Medicine
    Shanghai Jiaotong University School of Medicine)

  • Ken Yamamoto

    (Kurume University School of Medicine)

  • Toshimasa Yamauchi

    (The University of Tokyo)

  • Kyungheon Yoon

    (National Institute of Health)

  • Canqing Yu

    (Peking University)

  • Jian-Min Yuan

    (University of Pittsburgh
    University of Pittsburgh)

  • Liang Zhang

    (Singapore National Eye Centre)

  • Wei Zheng

    (Vanderbilt University Medical Center)

  • Michiya Igase

    (Ehime University Graduate School of Medicine)

  • Yoon Shin Cho

    (Hallym University)

  • Jerome I. Rotter

    (The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
    Harbor-UCLA Medical Center)

  • Ya-Xing Wang

    (Capital Medical University)

  • Wayne H. H. Sheu

    (National Defense Medical Center
    National Yang-Ming University
    Taichung Veterans General Hospital)

  • Mitsuhiro Yokota

    (Kurume University School of Medicine)

  • Jer-Yuarn Wu

    (Academia Sinica)

  • Ching-Yu Cheng

    (Singapore National Eye Centre
    Duke-NUS Medical School
    National University of Singapore and National University Health System)

  • Tien-Yin Wong

    (Singapore National Eye Centre
    Duke-NUS Medical School
    National University of Singapore and National University Health System)

  • Xiao-Ou Shu

    (Vanderbilt University Medical Center)

  • Norihiro Kato

    (National Center for Global Health and Medicine)

  • Kyong-Soo Park

    (Seoul National University Hospital
    Seoul National University College of Medicine
    Seoul National University)

  • E-Shyong Tai

    (National University of Singapore and National University Health System
    National University of Singapore and National University Health System
    Duke-NUS Medical School)

  • Fumihiko Matsuda

    (Kyoto University Graduate School of Medicine)

  • Woon-Puay Koh

    (National University of Singapore and National University Health System
    Duke-NUS Medical School)

  • Ronald C. W. Ma

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong
    The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Shiro Maeda

    (RIKEN Centre for Integrative Medical Sciences
    University of the Ryukyus
    University of the Ryukyus Hospital)

  • Iona Y. Millwood

    (University of Oxford
    University of Oxford)

  • Juyoung Lee

    (National Institute of Health)

  • Takashi Kadowaki

    (The University of Tokyo)

  • Robin G. Walters

    (University of Oxford
    University of Oxford)

  • Bong-Jo Kim

    (National Institute of Health)

  • Karen L. Mohlke

    (University of North Carolina at Chapel Hill)

  • Xueling Sim

    (National University of Singapore and National University Health System)

Abstract

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes—NKX6-3 and ANK1—in different tissues4–6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.

Suggested Citation

  • Cassandra N. Spracklen & Momoko Horikoshi & Young Jin Kim & Kuang Lin & Fiona Bragg & Sanghoon Moon & Ken Suzuki & Claudia H. T. Tam & Yasuharu Tabara & Soo-Heon Kwak & Fumihiko Takeuchi & Jirong Long, 2020. "Identification of type 2 diabetes loci in 433,540 East Asian individuals," Nature, Nature, vol. 582(7811), pages 240-245, June.
    • Handle: RePEc:nat:nature:v:582:y:2020:i:7811:d:10.1038_s41586-020-2263-3
    DOI: 10.1038/s41586-020-2263-3
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    Citations

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    Cited by:

    1. Yi-Jia Huang & Chun-houh Chen & Hsin-Chou Yang, 2024. "AI-enhanced integration of genetic and medical imaging data for risk assessment of Type 2 diabetes," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Léon Gurp & Leon Fodoulian & Daniel Oropeza & Kenichiro Furuyama & Eva Bru-Tari & Anh Nguyet Vu & John S. Kaddis & Iván Rodríguez & Fabrizio Thorel & Pedro L. Herrera, 2022. "Generation of human islet cell type-specific identity genesets," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Tzu-Ting Chen & Jaeyoung Kim & Max Lam & Yi-Fang Chuang & Yen-Ling Chiu & Shu-Chin Lin & Sang-Hyuk Jung & Beomsu Kim & Soyeon Kim & Chamlee Cho & Injeong Shim & Sanghyeon Park & Yeeun Ahn & Aysu Okbay, 2024. "Shared genetic architectures of educational attainment in East Asian and European populations," Nature Human Behaviour, Nature, vol. 8(3), pages 562-575, March.
    4. Yi-Cheng Chang & Hsiao-Lin Lee & Wenjin Yang & Meng-Lun Hsieh & Cai-Cin Liu & Tung-Yuan Lee & Jing-Yong Huang & Jiun-Yi Nong & Fu-An Li & Hsiao-Li Chuang & Zhi-Zhong Ding & Wei-Lun Su & Li-Yun Chueh &, 2023. "A common East-Asian ALDH2 mutation causes metabolic disorders and the therapeutic effect of ALDH2 activators," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Yuki Ishikawa & Nao Tanaka & Yoshihide Asano & Masanari Kodera & Yuichiro Shirai & Mitsuteru Akahoshi & Minoru Hasegawa & Takashi Matsushita & Kazuyoshi Saito & Sei-ichiro Motegi & Hajime Yoshifuji & , 2024. "GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    6. Fengzhe Xu & Evan Yi-Wen Yu & Xue Cai & Liang Yue & Li-peng Jing & Xinxiu Liang & Yuanqing Fu & Zelei Miao & Min Yang & Menglei Shuai & Wanglong Gou & Congmei Xiao & Zhangzhi Xue & Yuting Xie & Sainan, 2023. "Genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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