Yoon Shin Cho, Chien-Hsiun Chen, Cheng Hu, Jirong Long, Rick Twee Hee Ong, Xueling Sim, Fumihiko Takeuchi, Ying Wu, Min Jin Go, Toshimasa Yamauchi, Yi-Cheng Chang, Soo Heon Kwak, Ronald C W Ma, Ken Yamamoto, Linda S Adair, Tin Aung, Qiuyin Cai, Li-Ching Chang, Yuan-Tsong Chen, Yutang Gao, Frank B Hu, Hyung-Lae Kim, Sangsoo Kim, Young Jin Kim, Jeannette Jen-Mai Lee, Nanette R Lee, Yun Li, Jian Jun Liu, Wei Lu, Jiro Nakamura, Eitaro Nakashima, Daniel Peng-Keat Ng, Wan Ting Tay, Fuu-Jen Tsai, Tien Yin Wong, Mitsuhiro Yokota, Wei Zheng, Rong Zhang, Congrong Wang, Wing Yee So, Keizo Ohnaka, Hiroshi Ikegami, Kazuo Hara, Young Min Cho, Nam H Cho, Tien-Jyun Chang, Yuqian Bao, Åsa K. Hedman, Andrew P Morris, Mark I McCarthy, Ryoichi Takayanagi, Kyong Soo Park, Weiping Jia, Lee-Ming Chuang, Juliana C N Chan, Shiro Maeda, Takashi Kadowaki, Jong-Young Lee, Jer-Yuarn Wu, Yik Ying Teo, E. Shyong Tai, Xiao Ou Shu, Karen L Mohlke, Norihiro Kato, Bok-Ghee Han, Mark Seielstad
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, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A 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.
Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Cheongwon-gun, Gangoe-myeon, Yeonje-ri, Chungcheongbuk-do, South Korea; Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Endocrinology and Metabolism, Shanghai Jiao Tong University, Affiliated Sixth People's Hospital, Shanghai, China; Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, United States; Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore, Singapore; Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore; Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan; Department of Genetics, University of North Carolina, Chapel Hill, NC, United States; Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, Seoul National University, College of Medicine, Seoul, South Korea; Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong; Division of Genome Analysis, Research Center for Genetic Information, Kyushu University, Higashi-ku, Fukuoka, Japan; Department of Nutrition, University of North Carolina, Chapel Hill, NC, United States; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; Department of Ophthalmology, National University of Singapore, Singapore, Singapore; Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China; Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, United States; Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, South Korea; School of Systems Biomedical Science, Soongsil University, Dongjak-gu, Seoul, South Korea; Department of Epidemiology and Public Health, National University of Singapore, Singapore, Singapore; Office of Population Studies Foundation Inc., University of San Carlos, Cebu City, Philippines; Department of Biostatistics, University of North Carolina, Chapel Hill, NC, United States; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore; Shanghai Institute of Preventive Medicine, Shanghai, China; Department of Internal Medicine, Nagoya University, Graduate School of Medicine, Nagoya, Japan; Department of Diabetes and Endocrinology, Chubu Rosai Hospital, Nagoya, Japan; Centre for Eye Research Australia, University of Melbourne, East Melbourne, VIC, Australia; Department of Genome Science, Aichi-Gakuin University, School of Dentistry, Nagoya, Japan; Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan; Department of Endocrinology, Metabolism and Diabetes, Kinki University, School of Medicine, Osaka-sayama, Osaka, Japan; Department of Preventive Medicine, Ajou University School of Medicine, Suwon, South Korea; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom; Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan; World Class University Program, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul, South Korea; Graduate Institute of Clinical Medicine, National Taiwan University, School of Medicine, Taipei, Taiwan; Laboratory for Endocrinology and Metabolism, RIKEN Center for Genomic Medicine, Yokohama, Japan; Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore; Department of Medicine, National University of Singapore, Singapore, Singapore; Duke-National University of Singapore, Graduate Medical School, Singapore, Singapore; Institute for Human Genetics, University of California, San Francisco, CA, United States; Blood Systems Research Institute, San Francisco, CA, United States
