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

View ORCID ProfileCassandra N Spracklen, Momoko Horikoshi, Young Jin Kim, Kuang Lin, Fiona Bragg, Sanghoon Moon, Ken Suzuki, Claudia HT Tam, Yasuharu Tabara, Soo-Heon Kwak, Fumihiko Takeuchi, Jirong Long, Victor JY Lim, Jin-Fang Chai, Chien-Hsiun Chen, Masahiro Nakatochi, Jie Yao, Hyeok Sun Choi, Apoorva K Iyengar, Hannah J Perrin, Sarah M Brotman, Martijn van de Bunt, Anna L Gloyn, Jennifer E Below, Michael Boehnke, Donald W Bowden, John C Chambers, Anubha Mahajan, Mark I McCarthy, Maggie CY Ng, Lauren E Petty, Weihua Zhang, Andrew P Morris, Linda S Adair, Zheng Bian, Juliana CN Chan, Li-Ching Chang, Miao-Li Chee, Yii-Der Ida Chen, Yuan-Tsong Chen, Zhengming Chen, Lee-Ming Chuang, Shufa Du, Penny Gordon-Larsen, Myron Gross, Xiuqing Guo, Yu Guo, Sohee Han, Annie-Green Howard, Wei Huang, Yi-Jen Hung, Mi Yeong Hwang, Chii-Min Hwu, Sahoko Ichihara, Masato Isono, Hye-Mi Jang, Guozhi Jiang, Jost B Jonas, Yoichiro Kamatani, Tomohiro Katsuya, Takahisa Kawaguchi, Chiea-Chuen Khor, Katsuhiko Kohara, Myung-Shik Lee, Nannette R Lee, Liming Li, Jianjun Liu, Andrea O Luk, Jun Lv, Yukinori Okada, Mark A Pereira, Charumathi Sabanayagam, Jinxiu Shi, Dong Mun Shin, Wing Yee So, Atsushi Takahashi, Brian Tomlinson, Fuu-Jen Tsai, Rob M van Dam, Yong-Bing Xiang, Ken Yamamoto, Toshimasa Yamauchi, Kyungheon Yoon, Canqing Yu, Jian-Min Yuan, Liang Zhang, Wei Zheng, Michiya Igase, Yoon Shin Cho, Jerome I Rotter, Ya-Xing Wang, Wayne HH Sheu, Mitsuhiro Yokota, Jer-Yuarn Wu, Ching-Yu Cheng, Tien-Yin Wong, Xiao-Ou Shu, Norihiro Kato, Kyong-Soo Park, E-Shyong Tai, Fumihiko Matsuda, Woon-Puay Koh, Ronald CW Ma, Shiro Maeda, Iona Y Millwood, Juyoung Lee, Takashi Kadowaki, Robin G Walters, Bong-Jo Kim, Karen L Mohlke, Xueling Sim
doi: https://doi.org/10.1101/685172
Cassandra N Spracklen
1Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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  • ORCID record for Cassandra N Spracklen
Momoko Horikoshi
2Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan
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Young Jin Kim
3Division of Genome Research, Center for Genome Science, National Institute of Health, Cheongjusi, Korea
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Kuang Lin
4Nuffield Department of Population Health, University of Oxford, Oxford, UK
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Fiona Bragg
4Nuffield Department of Population Health, University of Oxford, Oxford, UK
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Sanghoon Moon
3Division of Genome Research, Center for Genome Science, National Institute of Health, Cheongjusi, Korea
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Ken Suzuki
2Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan
5Laboratory for Statistical and Translational Genetics, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan
6Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
7Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan
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Claudia HT Tam
8Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
9Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong, China
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Yasuharu Tabara
10Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Soo-Heon Kwak
11Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
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Fumihiko Takeuchi
12Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
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Jirong Long
13Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
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Victor JY Lim
14Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
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Jin-Fang Chai
14Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
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Chien-Hsiun Chen
15Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
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Masahiro Nakatochi
16Department of Nursing, Nagoya University Graduate School of Medicine, Nagoya University Hospital, Nagoya, Japan
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Jie Yao
17Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA
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Hyeok Sun Choi
18Biomedical Science, Hallym University, Chuncheon, South Korea
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Apoorva K Iyengar
1Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Hannah J Perrin
1Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Sarah M Brotman
1Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Martijn van de Bunt
19Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
20Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
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Anna L Gloyn
19Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
20Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
21Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford, UK
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Jennifer E Below
22Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
23Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA
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Michael Boehnke
24Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA
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Donald W Bowden
25Center for Genomics and Personalized Medicine Research, Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA
26Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA
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John C Chambers
27Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
28Department of Epidemiology and Biostatistics, Imperial College London, London, UK
29Department of Cardiology, Ealing Hospital, London North West Healthcare NHS Trust, Middlesex, UK
30Imperial College Healthcare NHS Trust, Imperial College London, London, UK
31MRC-PHE Centre for Environment and Health, Imperial College London, London, UK
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Anubha Mahajan
19Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
20Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
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Mark I McCarthy
19Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
20Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
21Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford, UK
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Maggie CY Ng
22Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
25Center for Genomics and Personalized Medicine Research, Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA
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Lauren E Petty
22Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
23Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA
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Weihua Zhang
28Department of Epidemiology and Biostatistics, Imperial College London, London, UK
29Department of Cardiology, Ealing Hospital, London North West Healthcare NHS Trust, Middlesex, UK
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Andrew P Morris
20Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
32Department of Biostatistics, University of Liverpool, Liverpool, UK
33School of Biological Sciences, University of Manchester, Manchester, UK
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Linda S Adair
34Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Zheng Bian
35Chinese Academy of Medical Sciences, Beijing, China
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Juliana CN Chan
8Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
9Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong, China
36Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China
37Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
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Li-Ching Chang
15Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
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Miao-Li Chee
38Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore
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Yii-Der Ida Chen
17Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA
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Yuan-Tsong Chen
15Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
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Zhengming Chen
4Nuffield Department of Population Health, University of Oxford, Oxford, UK
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Lee-Ming Chuang
39Division of Endocrinology & Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
40Institute of Preventive Medicine, School of Public Health, National Taiwan University, Taipei, Taiwan
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Shufa Du
34Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Penny Gordon-Larsen
34Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Myron Gross
41Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
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Xiuqing Guo
17Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA
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Yu Guo
35Chinese Academy of Medical Sciences, Beijing, China
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Sohee Han
3Division of Genome Research, Center for Genome Science, National Institute of Health, Cheongjusi, Korea
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Annie-Green Howard
42Department of Biostatistics, Carolina Population Center, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Wei Huang
43Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China
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Yi-Jen Hung
44Division of Endocrine and Metabolism, Tri-Service General Hospital Songshan Branch, Taipei, Taiwan
45School of Medicine, National Defense Medical Center, Taipei, Taiwan
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Mi Yeong Hwang
3Division of Genome Research, Center for Genome Science, National Institute of Health, Cheongjusi, Korea
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Chii-Min Hwu
46Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
47School of Medicine, National Yang-Ming University, Taipei, Taiwan
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Sahoko Ichihara
48Department of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan
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Masato Isono
12Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
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Hye-Mi Jang
3Division of Genome Research, Center for Genome Science, National Institute of Health, Cheongjusi, Korea
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Guozhi Jiang
8Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
9Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong, China
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Jost B Jonas
49Department of Ophthalmology, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany
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Yoichiro Kamatani
5Laboratory for Statistical and Translational Genetics, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan
50Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
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Tomohiro Katsuya
51Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Osaka, Japan
52Department of Geriatric and General Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
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Takahisa Kawaguchi
10Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Chiea-Chuen Khor
53Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore
54Department of Biochemistry, National University of Singapore, Singapore, Singapore
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Katsuhiko Kohara
55Department of Regional Resource Management, Ehime University Faculty of Collaborative Regional Innovation, Ehime, Japan
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Myung-Shik Lee
56Severance Biomedical Science Institute and Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
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Nannette R Lee
57Department of Anthropology, Sociology and History, University of San Carlos, Cebu City, Philippines
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Liming Li
58Departments of Epidemiology & Biostatistics, Peking University Health Science Centre, Peking University, Beijing, China
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Jianjun Liu
53Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore
59Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore
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Andrea O Luk
8Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
9Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong, China
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Jun Lv
58Departments of Epidemiology & Biostatistics, Peking University Health Science Centre, Peking University, Beijing, China
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Yukinori Okada
7Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan
60Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Osaka, Japan
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Mark A Pereira
61Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA
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Charumathi Sabanayagam
38Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore
62Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore
63Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore
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Jinxiu Shi
43Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China
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Dong Mun Shin
3Division of Genome Research, Center for Genome Science, National Institute of Health, Cheongjusi, Korea
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Wing Yee So
8Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
36Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China
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Atsushi Takahashi
5Laboratory for Statistical and Translational Genetics, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan
64Department of Genomic Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
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Brian Tomlinson
8Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
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Fuu-Jen Tsai
65Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan
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Rob M van Dam
14Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
59Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore
66Department of Nutrition, Harvard T.H Chan School of Public Health, Boston, MA, USA
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Yong-Bing Xiang
67State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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Ken Yamamoto
68Department of Medical Biochemistry, Kurume University School of Medicine, Kurume, Japan
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Toshimasa Yamauchi
6Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Kyungheon Yoon
3Division of Genome Research, Center for Genome Science, National Institute of Health, Cheongjusi, Korea
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Canqing Yu
58Departments of Epidemiology & Biostatistics, Peking University Health Science Centre, Peking University, Beijing, China
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Jian-Min Yuan
69Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA
70Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
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Liang Zhang
38Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore
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Wei Zheng
13Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
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Michiya Igase
71Department of Anti-aging Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
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Yoon Shin Cho
18Biomedical Science, Hallym University, Chuncheon, South Korea
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Jerome I Rotter
72Departments of Pediatrics and Medicine, The Institute for Translational Genomics and Population Sciences, LA BioMed at Harbor-UCLA Medical Center, Torrance, CA, USA
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Ya-Xing Wang
73Beijing Institute of Ophthalmology, Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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Wayne HH Sheu
45School of Medicine, National Defense Medical Center, Taipei, Taiwan
47School of Medicine, National Yang-Ming University, Taipei, Taiwan
74Division of Endocrinology and Metabolism, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
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Mitsuhiro Yokota
75Kurume University School of Medicine, Kurume, Japan
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Jer-Yuarn Wu
15Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
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Ching-Yu Cheng
38Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore
62Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore
63Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore
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Tien-Yin Wong
38Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore
62Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore
63Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore
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Xiao-Ou Shu
13Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
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Norihiro Kato
12Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
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Kyong-Soo Park
11Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
76Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
77Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea
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E-Shyong Tai
14Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
59Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore
78Duke-NUS Medical School, Singapore, Singapore
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Fumihiko Matsuda
10Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Woon-Puay Koh
14Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
79Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore
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Ronald CW Ma
8Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
9Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong, China
36Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China
37Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
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Shiro Maeda
2Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan
80Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
81Division of Clinical Laboratory and Blood Transfusion, University of the Ryukyus Hospital, Okinawa, Japan
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Iona Y Millwood
4Nuffield Department of Population Health, University of Oxford, Oxford, UK
82Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK
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Juyoung Lee
3Division of Genome Research, Center for Genome Science, National Institute of Health, Cheongjusi, Korea
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Takashi Kadowaki
6Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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  • For correspondence: mohlke@med.unc.edu ephsx@nus.edu.sg
Robin G Walters
4Nuffield Department of Population Health, University of Oxford, Oxford, UK
82Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK
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  • For correspondence: mohlke@med.unc.edu ephsx@nus.edu.sg
Bong-Jo Kim
3Division of Genome Research, Center for Genome Science, National Institute of Health, Cheongjusi, Korea
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  • For correspondence: mohlke@med.unc.edu ephsx@nus.edu.sg
Karen L Mohlke
1Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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  • For correspondence: mohlke@med.unc.edu ephsx@nus.edu.sg
Xueling Sim
14Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
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  • For correspondence: mohlke@med.unc.edu ephsx@nus.edu.sg
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SUMMARY

Meta-analyses of genome-wide association studies (GWAS) have identified >240 loci associated with type 2 diabetes (T2D), however most loci have been identified in analyses of European-ancestry individuals. To examine T2D risk in East Asian individuals, we meta-analyzed GWAS data in 77,418 cases and 356,122 controls. In the main analysis, we identified 298 distinct association signals at 178 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 56 loci newly implicated in T2D predisposition. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. New associations include signals in/near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect muscle and adipose differentiation. At another locus, eQTLs at two overlapping T2D signals act through two genes, NKX6-3 and ANK1, in different tissues. Association studies in diverse populations identify additional loci and elucidate disease genes, biology, and pathways.

Type 2 diabetes (T2D) is a common metabolic disease primarily caused by insufficient insulin production and/or secretion by the pancreatic β cells and insulin resistance in peripheral tissues1. Most genetic loci associated with T2D have been identified in populations of European (EUR) ancestry, including a recent meta-analysis of genome-wide association studies (GWAS) of nearly 900,000 individuals of European ancestry that identified >240 loci influencing the risk of T2D2. Differences in allele frequency between ancestries affect the power to detect associations within a population, particularly among variants rare or monomorphic in one population but more frequent in another3,4. Although smaller than studies in European populations, a recent T2D meta-analysis in almost 200,000 Japanese individuals identified 28 additional loci4. The relative contributions of different pathways to the pathophysiology of T2D may also differ between ancestry groups. For example, in East Asian (EAS) populations, T2D prevalence is greater than in European populations among people of similar body mass index (BMI) or waist circumference5. We performed the largest meta-analysis of East Asian individuals to identify new genetic associations and provide insight into T2D pathogenesis.

Footnotes

  • ↵84 These authors jointly supervised this work.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Identification of type 2 diabetes loci in 433,540 East Asian individuals
Cassandra N Spracklen, Momoko Horikoshi, Young Jin Kim, Kuang Lin, Fiona Bragg, Sanghoon Moon, Ken Suzuki, Claudia HT Tam, Yasuharu Tabara, Soo-Heon Kwak, Fumihiko Takeuchi, Jirong Long, Victor JY Lim, Jin-Fang Chai, Chien-Hsiun Chen, Masahiro Nakatochi, Jie Yao, Hyeok Sun Choi, Apoorva K Iyengar, Hannah J Perrin, Sarah M Brotman, Martijn van de Bunt, Anna L Gloyn, Jennifer E Below, Michael Boehnke, Donald W Bowden, John C Chambers, Anubha Mahajan, Mark I McCarthy, Maggie CY Ng, Lauren E Petty, Weihua Zhang, Andrew P Morris, Linda S Adair, Zheng Bian, Juliana CN Chan, Li-Ching Chang, Miao-Li Chee, Yii-Der Ida Chen, Yuan-Tsong Chen, Zhengming Chen, Lee-Ming Chuang, Shufa Du, Penny Gordon-Larsen, Myron Gross, Xiuqing Guo, Yu Guo, Sohee Han, Annie-Green Howard, Wei Huang, Yi-Jen Hung, Mi Yeong Hwang, Chii-Min Hwu, Sahoko Ichihara, Masato Isono, Hye-Mi Jang, Guozhi Jiang, Jost B Jonas, Yoichiro Kamatani, Tomohiro Katsuya, Takahisa Kawaguchi, Chiea-Chuen Khor, Katsuhiko Kohara, Myung-Shik Lee, Nannette R Lee, Liming Li, Jianjun Liu, Andrea O Luk, Jun Lv, Yukinori Okada, Mark A Pereira, Charumathi Sabanayagam, Jinxiu Shi, Dong Mun Shin, Wing Yee So, Atsushi Takahashi, Brian Tomlinson, Fuu-Jen Tsai, Rob M van Dam, Yong-Bing Xiang, Ken Yamamoto, Toshimasa Yamauchi, Kyungheon Yoon, Canqing Yu, Jian-Min Yuan, Liang Zhang, Wei Zheng, Michiya Igase, Yoon Shin Cho, Jerome I Rotter, Ya-Xing Wang, Wayne HH Sheu, Mitsuhiro Yokota, Jer-Yuarn Wu, Ching-Yu Cheng, Tien-Yin Wong, Xiao-Ou Shu, Norihiro Kato, Kyong-Soo Park, E-Shyong Tai, Fumihiko Matsuda, Woon-Puay Koh, Ronald CW Ma, Shiro Maeda, Iona Y Millwood, Juyoung Lee, Takashi Kadowaki, Robin G Walters, Bong-Jo Kim, Karen L Mohlke, Xueling Sim
bioRxiv 685172; doi: https://doi.org/10.1101/685172
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Identification of type 2 diabetes loci in 433,540 East Asian individuals
Cassandra N Spracklen, Momoko Horikoshi, Young Jin Kim, Kuang Lin, Fiona Bragg, Sanghoon Moon, Ken Suzuki, Claudia HT Tam, Yasuharu Tabara, Soo-Heon Kwak, Fumihiko Takeuchi, Jirong Long, Victor JY Lim, Jin-Fang Chai, Chien-Hsiun Chen, Masahiro Nakatochi, Jie Yao, Hyeok Sun Choi, Apoorva K Iyengar, Hannah J Perrin, Sarah M Brotman, Martijn van de Bunt, Anna L Gloyn, Jennifer E Below, Michael Boehnke, Donald W Bowden, John C Chambers, Anubha Mahajan, Mark I McCarthy, Maggie CY Ng, Lauren E Petty, Weihua Zhang, Andrew P Morris, Linda S Adair, Zheng Bian, Juliana CN Chan, Li-Ching Chang, Miao-Li Chee, Yii-Der Ida Chen, Yuan-Tsong Chen, Zhengming Chen, Lee-Ming Chuang, Shufa Du, Penny Gordon-Larsen, Myron Gross, Xiuqing Guo, Yu Guo, Sohee Han, Annie-Green Howard, Wei Huang, Yi-Jen Hung, Mi Yeong Hwang, Chii-Min Hwu, Sahoko Ichihara, Masato Isono, Hye-Mi Jang, Guozhi Jiang, Jost B Jonas, Yoichiro Kamatani, Tomohiro Katsuya, Takahisa Kawaguchi, Chiea-Chuen Khor, Katsuhiko Kohara, Myung-Shik Lee, Nannette R Lee, Liming Li, Jianjun Liu, Andrea O Luk, Jun Lv, Yukinori Okada, Mark A Pereira, Charumathi Sabanayagam, Jinxiu Shi, Dong Mun Shin, Wing Yee So, Atsushi Takahashi, Brian Tomlinson, Fuu-Jen Tsai, Rob M van Dam, Yong-Bing Xiang, Ken Yamamoto, Toshimasa Yamauchi, Kyungheon Yoon, Canqing Yu, Jian-Min Yuan, Liang Zhang, Wei Zheng, Michiya Igase, Yoon Shin Cho, Jerome I Rotter, Ya-Xing Wang, Wayne HH Sheu, Mitsuhiro Yokota, Jer-Yuarn Wu, Ching-Yu Cheng, Tien-Yin Wong, Xiao-Ou Shu, Norihiro Kato, Kyong-Soo Park, E-Shyong Tai, Fumihiko Matsuda, Woon-Puay Koh, Ronald CW Ma, Shiro Maeda, Iona Y Millwood, Juyoung Lee, Takashi Kadowaki, Robin G Walters, Bong-Jo Kim, Karen L Mohlke, Xueling Sim
bioRxiv 685172; doi: https://doi.org/10.1101/685172

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