Yoon Shin Cho^1,46, Chien-Hsiun Chen^2,3,46, Cheng Hu^4,46, Jirong Long^5,46, Rick Twee Hee Ong^6,46, Xueling Sim^7,46, Fumihiko Takeuchi^8,46, Ying Wu^9,46, Min Jin Go^1,46, Toshimasa Yamauchi^10,46, Yi-Cheng Chang^11,46, Soo Heon Kwak^12,46, Ronald C W Ma^13,46, Ken Yamamoto^14,46, Linda S Adair¹⁵, Tin Aung^16,17, Qiuyin Cai⁵, Li-Ching Chang², Yuan-Tsong Chen², Yutang Gao¹⁸, Frank B Hu¹⁹, Hyung-Lae Kim^1,20, Sangsoo Kim²¹, Young Jin Kim¹, Jeannette Jen-Mai Lee²², Nanette R Lee²³, Yun Li^9,24, Jian Jun Liu²⁵, Wei Lu²⁶, Jiro Nakamura²⁷, Eitaro Nakashima^27,28, Daniel Peng-Keat Ng²², Wan Ting Tay¹⁶, Fuu-Jen Tsai³, Tien Yin Wong^16,17,29, 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 McCarthy^34,35, DIAGRAM Consortium³⁶, MuTHER Consortium³⁶, Ryoichi Takayanagi^37,47, Kyong Soo Park^12,38,47, Weiping Jia^4,47, Lee-Ming Chuang^11,39,47, Juliana C N Chan^13,47, Shiro Maeda^39,47, Takashi Kadowaki^10,47, Jong-Young Lee^1,47, Jer-Yuarn Wu^2,3,47, Yik Ying Teo^{6,7,22,25,41,47}, E Shyong Tai^22,42,43,47, Xiao Ou Shu^5,47, Karen L Mohlke^9,47, Norihiro Kato^8,47, Bok-Ghee Han^1,47 & Mark Seielstad^25,44,45,47

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 expression^{1, 2}, is known for its association with fasting glucose levels^{3, 4}. The evidence of an association with T2D for PEPD⁵ and HNF4A^{6, 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.