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Li, H.,Kilpelä,inen, 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.,Man Springer-Verlag 2012 Diabetologia Vol.55 No.4
<P><B>Aims/hypothesis</B></P><P><I>FTO</I> harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for <I>FTO</I> 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 <I>FTO</I> locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.</P><P><B>Methods</B></P><P>All studies published on the association between <I>FTO</I>-rs9939609 (or proxy [<I>r</I><SUP>2</SUP> > 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.</P><P><B>Results</B></P><P>The <I>FTO</I>-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (<I>p</I> = 9.0 × 10<SUP>−19</SUP>), overweight by 1.13-fold/allele (<I>p</I> = 1.0 × 10<SUP>−11</SUP>) and type 2 diabetes by 1.15-fold/allele (<I>p</I> = 5.5 × 10<SUP>−8</SUP>). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, <I>p</I> = 6.6 × 10<SUP>−5</SUP>). The <I>FTO</I>-rs9939609 minor allele increased BMI by 0.26 kg/m<SUP>2</SUP> per allele (<I>p</I> = 2.8 × 10<SUP>−17</SUP>), WHR by 0.003/allele (<I>p</I> = 1.2 × 10<SUP>−6</SUP>), and body fat percentage by 0.31%/allele (<I>p</I> = 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 <I>FTO</I> variation on obesity-related traits and type 2 diabetes was similar in the two populations.</P><P><B>Conclusions/interpretation</B></P><P><I>FTO</I> 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, <I>FTO</I> is also associated with type 2 diabetes independently of BMI.</P><P><B>Electronic supplementary material</B></P><P>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.</P>
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