Yoon Shin Cho1,46, Chien-Hsiun Chen2,3,46, Cheng Hu4,46, Jirong Long5,46, Rick Twee Hee Ong6,46, Xueling Sim7,46, Fumihiko Takeuchi8,46, Ying Wu9,46, Min Jin Go1,46, Toshimasa Yamauchi10,46, Yi-Cheng Chang11,46, Soo Heon Kwak12,46, Ronald C W Ma13,46, Ken Yamamoto14,46, Linda S Adair15, Tin Aung16,17, Qiuyin Cai5, Li-Ching Chang2, Yuan-Tsong Chen2, Yutang Gao18, Frank B Hu19, Hyung-Lae Kim1,20, Sangsoo Kim21, Young Jin Kim1, Jeannette Jen-Mai Lee22, Nanette R Lee23, Yun Li9,24, Jian Jun Liu25, Wei Lu26, Jiro Nakamura27, Eitaro Nakashima27,28, Daniel Peng-Keat Ng22, Wan Ting Tay16, Fuu-Jen Tsai3, Tien Yin Wong16,17,29, Mitsuhiro Yokota30, Wei Zheng5, Rong Zhang4, Congrong Wang4, Wing Yee So13, Keizo Ohnaka31, Hiroshi Ikegami32, Kazuo Hara10, Young Min Cho12, Nam H Cho33, Tien-Jyun Chang11, Yuqian Bao4, Asa K Hedman34, Andrew P Morris34, Mark I McCarthy34,35, DIAGRAM Consortium36, MuTHER Consortium36, Ryoichi Takayanagi37,47, Kyong Soo Park12,38,47, Weiping Jia4,47, Lee-Ming Chuang11,39,47, Juliana C N Chan13,47, Shiro Maeda39,47, Takashi Kadowaki10,47, Jong-Young Lee1,47, Jer-Yuarn Wu2,3,47, Yik Ying Teo6,7,22,25,41,47, E Shyong Tai22,42,43,47, Xiao Ou Shu5,47, Karen L Mohlke9,47, Norihiro Kato8,47, Bok-Ghee Han1,47 & Mark Seielstad25,44,45,47
1Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Cheongwon-gun, Gangoe-myeon, Yeonje-ri, Korea. 2Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei, Taiwan. 3School of Chinese Medicine, China Medical University, Taichung, Taiwan. 4Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China. 5Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. 6Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore, Singapore. 7Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore. 8Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan. 9Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. 10Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 11Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 12Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. 13Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China. 14Division of Genome Analysis, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan. 15Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina, USA. 16Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore. 17Department of Ophthalmology, National University of Singapore, Singapore, Singapore. 18Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China. 19Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. 20Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Korea. 21School of Systems Biomedical Science, Soongsil University, Dongjak-gu, Seoul, Korea. 22Department of Epidemiology and Public Health, National University of Singapore, Singapore, Singapore. 23Office of Population Studies Foundation Inc., University of San Carlos, Cebu City, Philippines. 24Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, USA. 25Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore. 26Shanghai Institute of Preventive Medicine, Shanghai, China. 27Division of Endocrinology and Diabetes, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan. 28Department of Diabetes and Endocrinology, Chubu Rosai Hospital, Nagoya, Japan. 29Centre for Eye Research Australia, University of Melbourne, East Melbourne, Victoria, Australia. 30Department of Genome Science, Aichi-Gakuin University, School of Dentistry, Nagoya, Japan. 31Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan. 32Department of Endocrinology, Metabolism and Diabetes, Kinki University School of Medicine, Osaka-sayama, Osaka, Japan. 33Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Korea. 34Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. 35Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK. 36A full list of members is provided in the Supplementary Note. 37Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan. 38World Class University program, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine, Seoul National University, Seoul, Korea. 39Graduate Institute of Clinical Medicine, National Taiwan University School of Medicine, Taipei, Taiwan. 40Laboratory for Endocrinology and Metabolism, RIKEN Center for Genomic Medicine, Yokohama, Japan. 41Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore. 42Department of Medicine, National University of Singapore, Singapore, Singapore. 43Duke-National University of Singapore Graduate Medical School, Singapore, Singapore. 44Institute for Human Genetics, University of California, San Francisco, California, USA. 45Blood Systems Research Institute, San Francisco, California, USA. 46These authors contributed equally to this work. 47These authors jointly directed this work. Correspondence should be addressed to Y.S.C., M.S. or E.S.T.
We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression1, 2, is known for its association with fasting glucose levels3, 4. The evidence of an association with T2D for PEPD5 and HNF4A6, 7 has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.