Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians
Creators: name: Yang, Z.
name: Chandak, G. R.
name: Wen, W.
name: Hu, R.
name: Ikegami, H.
name: Song, Y.
name: Takeuchi, F.
name: Kim, J. Y.
name: Hotta, K.
name: Fujisawa, T.
name: Nakashima, E.
name: Chan, J. C.
name: Lin, X.
name: Lu, W.
name: Gao, Y.
name: Kato, N.
name: Maeda, S.
name: Park, K. S.
name: Liu, L.
name: Kwak, S. H.
name: Imamura, M.
name: Been, L. F.
name: Yang, T.
name: Chuang, L.
name: Mani, K. R.
name: Daimon, M.
name: Dorajoo, R.
name: Karasawa, S.
name: Xiang, Y.
name: Deng, H.
name: Sekine, A.
name: Fall, C. H.D.
name: Liu, Y.
name: Chang, Y.
name: Zhou, D.
name: Yajnik, C. S.
name: Kilpeläinen, T. O.
name: Lam, K. S.L.
name: Joglekar, C. V.
name: Lee, N.
name: Chambers, J. C.
name: Yokota, M.
name: Cha, S.
name: Bao, W.
name: Kim, Y.
name: Zhu, J.
name: Ma, R. C.
name: Jia, W.
name: Liu, S.
name: Zheng, W.
name: Shu, X.
name: Sham, P. C.
name: Hu, C.
name: Zhang, W.
name: Li, H.
name: Liu, C.
name: Yamamoto, K.
name: Choi, B. Y.
name: Shin, H. D.
name: Kooner, J. S.
name: Wu, Y.
name: Krishnaveni, G. V.
name: Takayanagi, R.
name: Sanghera, D. K.
name: Loos, R. J.F.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: Aims/hypothesisFTO 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.MethodsAll 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.ResultsThe 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 0.26kg/m2 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/interpretationFTO 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-011-2370-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.