Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians Public Deposited

Downloadable Content

Download PDF
Creator
  • MuTHER Consortium
  • Zhang, Rong
    • Other Affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Han, Bok-Ghee
    • Other Affiliation: Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Cheongwon-gun, Gangoe-myeon, Yeonje-ri, Korea.
  • Chang, Tien-Jyun
    • Other Affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • Takeuchi, Fumihiko
    • Other Affiliation: Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan.
  • Wu, Ying
    • Affiliation: School of Medicine, Department of Genetics
  • Ng, Daniel Peng-Keat
    • Other Affiliation: Department of Epidemiology and Public Health, National University of Singapore, Singapore, Singapore.
  • Chan, Juliana C.N.
    • Other Affiliation: Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
  • McCarthy, Mark I.
    • Other Affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
  • Chang, Li-Ching
    • Other Affiliation: Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei, Taiwan.
  • DIAGRAM Consortium
  • Shu, Xiao Ou
    • Other Affiliation: Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
  • Kadowaki, Takashi
    • Other Affiliation: Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Go, Min Jin
    • Other Affiliation: Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Cheongwon-gun, Gangoe-myeon, Yeonje-ri, Korea.
  • Wu, Jer-Yuarn
    • Other Affiliation: Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei, Taiwan. School of Chinese Medicine, China Medical University, Taichung, Taiwan.
  • Kwak, Soo Heon
    • Other Affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
  • Kim, Hyung-Lae
    • Other Affiliation: Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Cheongwon-gun, Gangoe-myeon, Yeonje-ri, Korea. Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Korea.
  • Chang, Yi-Cheng
    • Other Affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • Maeda, Shiro
    • Other Affiliation: Graduate Institute of Clinical Medicine, National Taiwan University School of Medicine, Taipei, Taiwan.
  • Cho, Nam H.
    • Other Affiliation: Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Korea.
  • Long, Jirong
    • Other Affiliation: Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
  • Takayanagi, Ryoichi
    • Other Affiliation: Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
  • Sim, Xueling
    • Other Affiliation: Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore.
  • Tay, Wan Ting
    • Other Affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
  • Hara, Kazuo
    • Other Affiliation: Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Lee, Jeannette Jen-Mai
    • Other Affiliation: Department of Epidemiology and Public Health, National University of Singapore, Singapore, Singapore.
  • Zheng, Wei
    • Other Affiliation: Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
  • Kato, Norihiro
    • Other Affiliation: Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan.
  • Nakashima, Eitaro
    • Other Affiliation: Division of Endocrinology and Diabetes, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan. Department of Diabetes and Endocrinology, Chubu Rosai Hospital, Nagoya, Japan.
  • Yokota, Mitsuhiro
    • Other Affiliation: Department of Genome Science, Aichi-Gakuin University, School of Dentistry, Nagoya, Japan.
  • Park, Kyong Soo
    • Other Affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. World 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.
  • Yamauchi, Toshimasa
    • Other Affiliation: Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Teo, Yik Ying
    • Other Affiliation: Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore, Singapore. Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore. Department of Epidemiology and Public Health, National University of Singapore, Singapore, Singapore. Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore. Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore.
  • Ohnaka, Keizo
    • Other Affiliation: Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
  • Ma, Ronald C.W.
    • Other Affiliation: Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
  • Aung, Tin
    • Other Affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore. Department of Ophthalmology, National University of Singapore, Singapore, Singapore.
  • Gao, Yutang
    • Other Affiliation: Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
  • Chuang, Lee-Ming
    • Other Affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Graduate Institute of Clinical Medicine, National Taiwan University School of Medicine, Taipei, Taiwan.
  • Wong, Tien Yin
    • Other Affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore. Department of Ophthalmology, National University of Singapore, Singapore, Singapore. Centre for Eye Research Australia, University of Melbourne, East Melbourne, Victoria, Australia.
  • Hu, Cheng
    • Other Affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Bao, Yuqian
    • Other Affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Lu, Wei
    • Other Affiliation: Shanghai Institute of Preventive Medicine, Shanghai, China.
  • Hedman, Asa K.
    • Other Affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Chen, Yuan-Tsong
    • Other Affiliation: Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei, Taiwan.
  • Mohlke, Karen
    • Affiliation: School of Medicine, Department of Genetics
  • Adair, Linda
    • Affiliation: Gillings School of Global Public Health, Department of Nutrition
  • Jia, Weiping
    • Other Affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • Lee, Jong-Young
    • Other Affiliation: Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Cheongwon-gun, Gangoe-myeon, Yeonje-ri, Korea.
  • Morris, Andrew P.
    • Other Affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Hu, Frank B.
    • Other Affiliation: Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
  • Ikegami, Hiroshi
    • Other Affiliation: Department of Endocrinology, Metabolism and Diabetes, Kinki University School of Medicine, Osaka-sayama, Osaka, Japan.
  • Yamamoto, Ken
    • Other Affiliation: Division of Genome Analysis, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan.
  • Lee, Nanette R.
    • Other Affiliation: Office of Population Studies Foundation Inc., University of San Carlos, Cebu City, Philippines.
  • Kim, Sangsoo
    • Other Affiliation: School of Systems Biomedical Science, Soongsil University, Dongjak-gu, Seoul, Korea.
  • Seielstad, Mark
    • Other Affiliation: Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore. Institute for Human Genetics, University of California, San Francisco, California, USA. Blood Systems Research Institute, San Francisco, California, USA.
  • Ong, Rick Twee Hee
    • Other Affiliation: Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore, Singapore.
  • Liu, Jian Jun
    • Other Affiliation: Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
  • Tsai, Fuu-Jen
    • Other Affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.
  • Cai, Qiuyin
    • Other Affiliation: Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
  • Cho, Young Min
    • Other Affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
  • Kim, Young Jin
    • Other Affiliation: Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Cheongwon-gun, Gangoe-myeon, Yeonje-ri, Korea.
  • Chen, Chien-Hsiun
    • Other Affiliation: Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei, Taiwan. School of Chinese Medicine, China Medical University, Taichung, Taiwan.
  • Tai, E. Shyong
    • Other Affiliation: Department of Epidemiology and Public Health, 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.
  • Nakamura, Jirong
    • Other Affiliation: Division of Endocrinology and Diabetes, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Cho, Yoon Shin
    • Other Affiliation: Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Cheongwon-gun, Gangoe-myeon, Yeonje-ri, Korea.
  • Li, Yun
    • Affiliation: School of Medicine, Department of Genetics, Gillings School of Global Public Health, Department of Biostatistics
  • So, Wing Yee
    • Other Affiliation: Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
  • Wang, Congrong
    • Other Affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Abstract
  • 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.
Date of publication
Keyword
Identifier
  • doi:10.1038/ng.1019
  • 2-s2.0-84655162045
Related resource URL
Resource type
  • Journal Item
Rights statement
  • In Copyright
Journal title
  • Nature Genetics
Journal volume
  • 44
Journal issue
  • 1
Page start
  • 67
Page end
  • 72
Language
  • English
Version
  • Postprint
ISSN
  • 1061-4036
Parents:

This work has no parents.

Items