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

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...

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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer-Verlag 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296006/
https://www.ncbi.nlm.nih.gov/pubmed/22109280
http://dx.doi.org/10.1007/s00125-011-2370-7
Descripción
Sumario: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. 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.

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