Title: Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians.

Authors: Li, H; Kilpeläinen, T O; Liu, C; Zhu, J; Liu, Y; Hu, C; Yang, Z; Zhang, W; Bao, W; Cha, S; Wu, Y; Yang, T; Sekine, A; Choi, B Y; Yajnik, C S; Zhou, D; Takeuchi, F; Yamamoto, K; Chan, J C; Mani, K R; Been, L F; Imamura, M; Nakashima, E; Lee, N; Fujisawa, T; Karasawa, S; Wen, W; Joglekar, C V; Lu, W; Chang, Y; Xiang, Y; Gao, Y; Liu, S; Song, Y; Kwak, S H; Shin, H D; Park, K S; Fall, C H D; Kim, J Y; Sham, P C; Lam, K S L; Zheng, W; Shu, X; Deng, H; Ikegami, H; Krishnaveni, G V; Sanghera, D K; Chuang, L; Liu, L; Hu, R; Kim, Y; Daimon, M; Hotta, K; Jia, W; Kooner, J S; Chambers, J C; Chandak, G R; Ma, R C; Maeda, S; Dorajoo, R; Yokota, M; Takayanagi, R; Kato, N; Lin, X; Loos, R J F

Published In Diabetologia, (2012 Apr)

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.

PubMed ID: 22109280

MeSH Terms: No MeSH terms associated with this publication