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

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., 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. and Loos, R.J.F (2012) Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians. Diabetologia, 55 (4), 981-995. (doi:10.1007/s00125-011-2370-7). (PMID:22109280)

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.

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Contributors

Author: C.H. Fall

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