1. Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians
- Author
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Dharambir K. Sanghera, Hui Li, Norihiro Kato, K. R. Mani, Soo Heon Kwak, Yiqing Song, J. Zhu, Y. Liu, T. Yang, Giriraj R. Chandak, Daizhan Zhou, Ryoichi Takayanagi, Tuomas O. Kilpeläinen, Lee-Ming Chuang, Ronald C.W. Ma, J. Y. Kim, Weihua Zhang, C. V. Joglekar, Zhen Yang, Ching-Ti Liu, B. Y. Choi, Yu-Tang Gao, C. S. Yajnik, Nanette R. Lee, S. Cha, Eitaro Nakashima, John C. Chambers, H. Deng, Wanqing Wen, Akihiro Sekine, Kyoung-Chan Park, Wei Jia, Karen Siu-Ling Lam, Juliana C.N. Chan, Yong-Bing Xiang, Wei Lu, Ruth J. F. Loos, Yi-Cheng Chang, Hyoung Doo Shin, Ken Yamamoto, Ghattu V. Krishnaveni, Fumihiko Takeuchi, Renming Hu, Makoto Daimon, Kikuko Hotta, Wei Bao, Jaspal S. Kooner, M Imamura, Caroline H.D. Fall, Wei Zheng, Tomomi Fujisawa, Simin Liu, Mitsuhiro Yokota, Latonya F. Been, Xu(林旭) Lin, Shiro Maeda, Lianqing Liu, Xiao-Ou Shu, Cheng Hu, Rajkumar Dorajoo, Y. Kim, Shigeru Karasawa, Hiroshi Ikegami, Pak C. Sham, Ying Wu, and Medical Research Council (MRC)
- Subjects
Male ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,LOCI ,Type 2 diabetes ,VARIANTS ,Diabetes Mellitus, Type 2 - genetics ,Obesity - genetics ,0302 clinical medicine ,ADULT OBESITY ,Genetics ,0303 health sciences ,pathological conditions, signs and symptoms ,3. Good health ,Asians ,FAT MASS ,Meta-analysis ,Obesity. Type 2 diabetes ,Female ,FTO ,Life Sciences & Biomedicine ,WAIST CIRCUMFERENCE ,Asian Continental Ancestry Group ,Adult ,South asia ,Genotype ,Alpha-Ketoglutarate-Dependent Dioxygenase FTO ,030209 endocrinology & metabolism ,Locus (genetics) ,Obesity risk ,Polymorphism, Single Nucleotide ,1117 Public Health and Health Services ,Endocrinology & Metabolism ,03 medical and health sciences ,Asian People ,Genetic variation ,Internal Medicine ,medicine ,Humans ,JAPANESE POPULATION ,Genetic Predisposition to Disease ,Obesity ,GENOME-WIDE ASSOCIATION ,METAANALYSIS ,Genetic Association Studies ,030304 developmental biology ,CHINESE POPULATION ,Science & Technology ,business.industry ,Proteins ,nutritional and metabolic diseases ,1103 Clinical Sciences ,Human physiology ,medicine.disease ,BODY-MASS INDEX ,Asian Continental Ancestry Group - genetics ,Diabetes Mellitus, Type 2 ,1114 Paediatrics and Reproductive Medicine ,Proteins - genetics ,business ,Demography - 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 [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., published_or_final_version, Springer Open Choice, 25 May 2012
- Published
- 2012