Association of Genetic Variation in \(FTO\) with Risk of Obesity and Type 2 Diabetes with Data from 96,551 East and South Asians

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Association of Genetic Variation in \(FTO\) with Risk of Obesity and Type 2 Diabetes with Data from 96,551 East and South Asians

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Title: Association of Genetic Variation in \(FTO\) with Risk of Obesity and Type 2 Diabetes with Data from 96,551 East and South Asians
Author: Kilpeläinen, T. O.; Sekine, A.; Yajnik, C. S.; Takeuchi, F.; Yamamoto, K.; Mani, K. R.; Been, L. F.; Imamura, M.; Nakashima, E.; Fujisawa, T.; Karasawa, S.; Joglekar, C. V.; Fall, C. H. D.; Sham, P. C.; Shu, X.; Deng, H.; Ikegami, H.; Krishnaveni, G. V.; Sanghera, D. K.; Chuang, L.; Daimon, M.; Hotta, K.; Kooner, J. S.; Chandak, G. R.; Maeda, S.; Dorajoo, R.; Yokota, M.; Takayanagi, R.; Loos, R. J. F.; Song, Yiqing; Li, H.; Liu, C.; Zhu, J.; Liu, Y.; Hu, C.; Yang, Z.; Zhang, W.; Bao, W.; Cha, S.; Wu, Y.; Yang, T.; Choi, B. Y.; Zhou, D.; Chan, J. C.; Lee, N.; Wen, W.; Lu, W.; Chang, Y.; Xiang, Y.; Gao, Y.; Liu, S.; Song, Yiqing; Kwak, S. H.; Shin, H. D.; Park, K. S.; Kim, J. Y.; Lam, K. S. L.; Zheng, W.; Liu, L.; Hu, R.; Kim, Y.; Jia, W.; Chambers, J. C.; Ma, R. C.; Kato, N.; Lin, X.

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Citation: Li, H., T. O. Kilpeläinen, C. Liu, J. Zhu, Y. Liu, C. Hu, Z. Yang, et al. 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.
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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/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/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. Electronic supplementary material The 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.
Published Version: doi:10.1007/s00125-011-2370-7
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