Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians
Year: 2011
Type: review
Abstract: 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 [r (2) > 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.
Source: Diabetologia
Authors: 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
Institutions: Chinese Academy of Sciences, Shanghai Institutes for Biological Sciences, Addenbrooke's Hospital, MRC Epidemiology Unit, Fudan University, Shanghai Jiao Tong University, Shanghai Sixth People's Hospital, Shanghai Medical College of Fudan University, Huashan Hospital, Imperial College London, Huazhong University of Science and Technology, Korea Institute of Oriental Medicine, University of North Carolina at Chapel Hill, Xi'an Jiaotong University, Kyoto University, National Center for Global Health and Medicine, Kyushu University, Medical Institute of Bioregulation, Kyushu University, Chinese University of Hong Kong, Prince of Wales Hospital, Centre for Cellular and Molecular Biology, University of Oklahoma Health Sciences Center, Chubu Rosai Hospital, University of San Carlos, The University of Osaka, Yamagata University, Vanderbilt University, National Taiwan University Hospital, Shanghai Cancer Institute, University of California, Los Angeles, Brigham and Women's Hospital, Harvard University, Seoul National University, Sogang University, Southampton General Hospital, MRC Lifecourse Epidemiology Unit, University of Southampton, University of Hong Kong, University of Shanghai for Science and Technology, Beijing Jiaotong University, University of Missouri–Kansas City, Kindai University, CSI Holdsworth Memorial Hospital, Dong-A University, Hammersmith Hospital, Agency for Science, Technology and Research, Genome Institute of Singapore, Aichi Gakuin University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,490
Funders: U.S. Department of Health and Human Services, Wellcome Trust, National Institute for Health and Care Research, British Heart Foundation, Imperial College London, Imperial College Healthcare NHS Trust, National Research Foundation, Council of Scientific and Industrial Research, India, National Natural Science Foundation of China, National Science Council, Ministry of Education of the People's Republic of China, Chinese Academy of Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, National Research Foundation of Korea, Chinese University of Hong Kong, Innovation and Technology Fund, Hong Kong Government, National Institutes of Health, Directorate for Biological Sciences, Medical Research Council, Japan Society for the Promotion of Science, Program for New Century Excellent Talents in University, Shanghai Leading Academic Discipline Project, National High-tech Research and Development Program, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Heart, Lung, and Blood Institute, National Cancer Institute, Fogarty International Center, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources
Awards: G109231058, G1107292973, Women's Health Initiative, Identification of genetic variants underlying coronary artery disease and associated phenotypes in Indian Asians., G1226609078, Organ specificity in autoimmune diseases: beta-cells and type 1 diabetes, Women's Health Initiative, Shanghai Breast Cancer Study, G156924709, Women's Health Initiative, G1593340546, G1617453120, G1646017446, G1828425977, Genetic Epidemiology of Body Mass Index, Adiposity and Weight Gain, Weight, Diet, Genes and CVD Risk Factors (Hypertension and Diabetes), G1968135291, The strategy for elucidation of diabetogenic factors:functional partition and reintegrate, G206718646, Investigation on the association between the taste receptor gene polymorphisms, incretin secretion and metabolic disorders involved in eating behavior, G2111063131, Early-life antecedents of type 2 diabetes and polycystic ovary syndrome in young Indian adults., Women's Health Initiative, G2153633957, G2253702613, G227387708, G2286437695, G2290742579, G2295046671, Genome-wide Association Scan to Identify Risk Genes for Type 2 Diabetes in Asian, G2417273319, G2520421342, Genetic and Biochemical Predictors of Type 2 DM in Women, G2547046739, G2553430561, G257474614, G2848036350, G2852769941, G2880260212, Cancer Risk Reduction and Diet: A Cohort Study of Women, G2939443841, G3253097015, Women's Health Initiative Memory Study (WHIMS), G347424564, Genomic Convergence for Female Osteoporosis Risk Genes, G3536174877, G3544793024, Women's Health Initiative, Genomic search for bone mass QTLs, G3642616392, Biochemical Predictors of Type 2 DM in Women, G3897472563, PTH和IL21R基因多态性与骨质疏松症的遗传关联研究, Women's Health Initiative, Women's Health Initiative, G4125898295, G413560588, Indo-US Collaboration in Genomic Studies on Diabetes, G4214622172, G4216744017, G422232192, G4243412236, G4281851297, COORDINATING CENTER FOR WOMEN'S HEALTH INITIATIVE, G429396632, G4321061599, G439563547, G445374210, G4454202622, G4503149662, G4560602636, G4813860285, G484043965, G4867292756, G4940723635, Prediction of the genetic risk associated with lifestyle-related diseases in a population based cohort study, Robust and Powerful Test of Candidate Genes to Bone Mass, G5183277930, Cohort Study of Cancer-Inhibitory Dietary Factors in Men, FOR ALL FIELD CENTER FOR WHI EXTENSION, G530368906, G532295152, G5404300429, G555506801, DNA拷贝数变异和肥胖症的遗传关联研究, G603760282, Alcohol Dependence Genetics in a Large Chinese Pedigree, G6140193975, G6206675870, G633297803, An Interdisciplinary Strategy for Obesity (RMI), G6464247198, Identification of genetic variants underlying coronary artery disease and associated phenotypes in Indian Asians., G6758477158, Women's Health Initiative, 天然抗氧化剂姜黄素防治2型糖尿病及Nrf2/HO-1介导的机制研究, G6815174083, 中国人2型糖尿病全基因组关联研究中发现易感位点的大样本关联研究, G7066869570, G7071300326, Obesity development and CVD risk factor clustering in Filipino women & offspring, G7223985928, Effect of Health on Education &Work in Filipino Youth, G7272550893, Women's Health Initiative, G7323080267, G7582705761, Derivation and validation of a risk model for prediction of cardiovascular disease events in UK Indian Asians, G80800813, Developmental programming of adiposity and insulin resistance in rural and urban Indian children, and pilot work to explore its reversibility during adolescent growth., Identification of Proteins Important for Male Osteoporosis, 基因与环境因素相互作用对2型糖尿病发病的影响研究, The material origins of type-2 diabetes in India., G8780700017, G8934942062, G8937465282, G9000002220, G9000015938, G9000016408, G9000029166, G9000039219, G9000072420, G9000075712, G9000099044, G9000131094, G9000151586, G9000281921, UNC Center for Environmental Health and Susceptibility, Nutrition Obesity Research Center (NORC), Proteomics Study of Peripheral Blood Monocytes on Osteoporosis, G999174792
OpenAlex ID: W2121819193