H. Li, T.O. Kilpeläinen, C. Liu, J. Zhu, Y. Liu, C. Hu, Z. Yang, W. Zhang, W. Bao, S. Cha, Y. Wu, T. Yang, A. Sekine, B.Y. Choi, C.S. Yajnik, D. Zhou, F. Takeuchi, K. Yamamoto, J.C. Chan, K.R. Mani, L.F. Been, M. Imamura, E. Nakashima, N. Lee, T. Fujisawa, S. Karasawa, W. Wen, C.V. Joglekar, W. Lu, Y. Chang, Y. Xiang, Y. Gao, S. Liu, Y. Song, S.H. Kwak, H.D. Shin, K.S. Park, C.H.D. Fall, J.Y. Kim, P.C. Sham, K.S.L. Lam, W. Zheng, X. Shu, H. Deng, H. Ikegami, G.V. Krishnaveni, D.K. Sanghera, L. Chuang, L. Liu, R. Hu, Y. Kim, M. Daimon, K. Hotta, W. Jia, J.S. Kooner, J.C. Chambers, G.R. Chandak, R.C. Ma, S. Maeda, R. Dorajoo, M. Yokota, R. Takayanagi, N. Kato, X. Lin, R.J.F. Loos
Aims/hypothesis FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. Methods All studies published on the association between FTO-rs9939609 (or proxy [r2>0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. Results The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p=9.0×10 -19), overweight by 1.13-fold/allele (p=1.0×10 -11) and type 2 diabetes by 1.15-fold/allele (p=5.5×10 -8). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p=6.6×10 -5). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m 2 per allele (p=2.8×10 -17), WHR by 0.003/allele (p=1.2×10 -6), and body fat percentage by 0.31%/allele (p=0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12-20%) than South Asians (30-33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations. Conclusions/interpretation FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI. © 2012 Springer-Verlag.
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, 294 Tai-Yuan Road, China; MRC Epidemiology Unit, Institute of Metabolic Science Box 285, Addenbrooke's Hospital, Cambridge CB2 0QQ, Hills Road, United Kingdom; Institutes of Biomedical Sciences, Fudan University, Shanghai, China; Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China; Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Shanghai, China; Department Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Nutrition and Food Hygiene, School of Public Health, Huazhong University of Science and Technology, Wuhan, China; Division of Constitutional Medicine Research, Korea Institute of Oriental Medicine, Daejeon, South Korea; Department of Genetics, University of North Carolina, Chapel Hill, NC, United States; Key Laboratory of Biomedical Information Engineering of, School of Life Science and Technology, Xi'An Jiaotong University, Xi'an, China; EBM Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Preventive Medicine, HanYang University College of Medicine, Seoul, South Korea; Diabetology Research Centre, KEM Hospital and Research Centre, Pune, India; National Center for Global Health and Medicine, Tokyo, Japan; Division of Genome Analysis, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong; Centre for Cellular and Molecular Biology (CCMB-CSIR), Hyderabad, India; University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Laboratory for Endocrinology and Metabolism, RIKEN Center for Genomic Medicine, Yokohama, Japan; Department of Diabetes and Endocrinology, Chubu Rosai Hospital, Nagoya, Japan; USC Office of Population Studies Foundation, University of San Carlos, Cebu, Philippines; Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Japan; Third Department of Internal Medicine, Global Center of Excellence Program Study Group, Yamagata University School of Medicine, Yamagata, Japan; Division of Epidemiology, Department of Medicine, Vanderbilt School of Medicine, Nashville, TN, United States; Shanghai Institute of Preventive Medicine, Shanghai, China; National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan; Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China; Center for Metabolic Disease Prevention, School of Public Health, David Geffen School of Medicine, Los Angeles, CA, United States; Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Department of Internal Medicine, Seoul National University, College of Medicine, Seoul, South Korea; Department of Life Science, Sogang University, Seoul, South Korea; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, Hampshire, United Kingdom; Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong; School of Medicine, University of Missouri, Kansas City, MO, United States; Center of Systematic Biomedical Research, University of Shanghai for Science and Technology, Shanghai, China; Institute of Bioscience and Biotechnology, School of Science, Beijing Jiaotong University, Beijing, China; Department of Endocrinology, Metabolism and Diabetes, Kinki University School of Medicine, Osaka, Japan; Epidemiology Research Unit, Holdsworth Memorial Hospital, Mysore, India; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Preventive Medicine, Dong-A University College of Medicine, Busan, South Korea; National Heart and Lung Institute, Hammersmith Hospital, Hammersmith Campus, London, United Kingdom; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore; Department of Genomics of Common Disease, School of Public Health, Hammersmith Hospital, London, United Kingdom; Department of Genome Science, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan; Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
