Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians.
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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FTO 遗传变异与肥胖和 2 型糖尿病风险的关联，数据来自 96,551 名东亚和南亚人
DOI：
10.1007/s00125-011-2370-7
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发表时间：
2012-04
期刊：
影响因子：
8.2
通讯作者：
Loos, R. J. F.
中科院分区：
文献类型：
--
作者：
Li, H.;Kilpelaeinen, 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.
目的/假设FTO是欧洲人中已知的最强烈的肥胖易感基因。虽然越来越多的证据表明FTO在亚洲人的肥胖风险中发挥了作用，但它与2型糖尿病的关联，独立于BMI，仍然不一致。为了检验FTO基因与肥胖和2型糖尿病是否存在关联，我们对包括96,551名东亚人和南亚人在内的32个人群进行了荟萃分析。方法邀请了所有已发表的关于FTO-rs9939609(或替代物[R2 >； 0.98])与东亚或南亚人体重指数、肥胖症或2型糖尿病之间关系的研究。每个研究组根据标准化的分析计划分析他们的数据。与2型糖尿病的关系也根据BMI进行了调整。结果FTO-rs9939609等位基因使肥胖风险增加1.25倍/等位基因(p = 9.0 × 10−19)，超重增加1.13倍/等位基因(p = 1.0 × 10−11)，2型糖尿病增加1.15倍/等位基因(p = 5.5 × 10−8)。调整体重指数后，与2型糖尿病的关联减弱(OR1.10倍/等位基因，p = 6.6 × 10−5)。体重指数增加0.26 kg/m2(p = 2.8 × 10−17)，腰臀比增加0.003个/等位基因(p = 1.2 × 10−6)，体脂百分比增加0.31%/等位基因(p = 0.0005)。使用显性模型时，关联性相似。虽然东亚人(12-20%)的微小等位基因比南亚人(30%-33%)少，但FTO基因变异对肥胖相关性状和2型糖尿病的影响在两个人群中相似。结论/解释此外，FTO还独立于BMI与2型糖尿病相关。
Aims/hypothesisFTO 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.MethodsAll studies published on the association between FTO-rs9939609 (or proxy [r2 > 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.ResultsThe 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 Furthermore, FTO is also associated with type 2 diabetes independently of BMI.
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影响因子：
30.8
作者：
通讯作者：
--
影响因子：
4.5
作者：
Heard-Costa NL;Zillikens MC;Monda KL;Johansson A;Harris TB;Fu M;Haritunians T;Feitosa MF;Aspelund T;Eiriksdottir G;Garcia M;Launer LJ;Smith AV;Mitchell BD;McArdle PF;Shuldiner AR;Bielinski SJ;Boerwinkle E;Brancati F;Demerath EW;Pankow JS;Arnold AM;Chen YD;Glazer NL;McKnight B;Psaty BM;Rotter JI;Amin N;Campbell H;Gyllensten U;Pattaro C;Pramstaller PP;Rudan I;Struchalin M;Vitart V;Gao X;Kraja A;Province MA;Zhang Q;Atwood LD;Dupuis J;Hirschhorn JN;Jaquish CE;O'Donnell CJ;Vasan RS;White CC;Aulchenko YS;Estrada K;Hofman A;Rivadeneira F;Uitterlinden AG;Witteman JC;Oostra BA;Kaplan RC;Gudnason V;O'Connell JR;Borecki IB;van Duijn CM;Cupples LA;Fox CS;North KE
通讯作者：
North KE
影响因子：
30.8
作者：
Chambers, John C.;Elliott, Paul;Kooner, Jaspal S.
通讯作者：
Kooner, Jaspal S.
影响因子：
5.8
作者：
Cheung, Chloe Y. Y.;Tso, Annette W. K.;Lam, Karen S. L.
通讯作者：
Lam, Karen S. L.
影响因子：
4.9
作者：
Dorajoo, R.;Blakemore, A. I. F.;Tai, E-S
通讯作者：
Tai, E-S