Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index.
Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index.
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DOI：
10.1093/ije/dyr077
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发表时间：
2011-12
影响因子：
7.7
通讯作者：
Munafò M
中科院分区：
文献类型：
--
作者：
Freathy RM;Kazeem GR;Morris RW;Johnson PC;Paternoster L;Ebrahim S;Hattersley AT;Hill A;Hingorani AD;Holst C;Jefferis BJ;Kring SI;Mooser V;Padmanabhan S;Preisig M;Ring SM;Sattar N;Upton MN;Vollenweider P;Waeber G;Sørensen TI;Frayling TM;Watt G;Lawlor DA;Whincup PH;Tozzi F;Davey Smith G;Munafò M
背景吸烟与较低的体重指数（BMI）有关，不愿意戒烟的一个常见原因是担心体重增加。CHRNA 5-CHRNA 3-CHRNB 4基因区域（染色体15 q25）的常见变异与吸烟者的吸烟量密切相关，但其与BMI的相关性尚不清楚。我们假设基因型能准确地反映吸烟暴露，如果吸烟与体重有因果关系，那么它与吸烟者的BMI相关，但与从不吸烟者的BMI无关。方法我们根据吸烟状况对9个欧洲研究样本进行分层，并在每个分层中分析15 q25 SNP，rs 1051730和BMI基因型之间的关联。我们对结果进行了荟萃分析（n = 24198），然后测试了基因型×吸烟状态的相互作用。结果没有证据表明从不吸烟者的BMI和基因型之间存在关联{每个T等位基因的差异：0.05 kg/m2 [95%置信区间（95%CI）：-0.05至0.18]; P = 0.25}。然而，在曾经吸烟者中，每增加一个吸烟相关的T等位基因，BMI就会降低0.23 kg/m2（95% CI：0.13-0.31）（P = 8 × 10−6）。目前的效应量[每个T等位基因的BMI降低0.33 kg/m2（95% CI：0.18-0.48）; P = 6 × 10−5]大于既往吸烟者[0.16 kg/m2（95% CI：0.03-0.29）; P = 0.01]。有强有力的证据表明基因型×吸烟交互作用（P = 0.0001）。结论吸烟状态改变了15 q25变异与BMI之间的关联，这加强了吸烟暴露与BMI降低有因果关系的证据。如果戒烟计划包括支持保持健康的BMI，那么戒烟计划可能会更成功。
Background Cigarette smoking is associated with lower body mass index (BMI), and a commonly cited reason for unwillingness to quit smoking is a concern about weight gain. Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region (chromosome 15q25) is robustly associated with smoking quantity in smokers, but its association with BMI is unknown. We hypothesized that genotype would accurately reflect smoking exposure and that, if smoking were causally related to weight, it would be associated with BMI in smokers, but not in never smokers. Methods We stratified nine European study samples by smoking status and, in each stratum, analysed the association between genotype of the 15q25 SNP, rs1051730, and BMI. We meta-analysed the results (n = 24 198) and then tested for a genotype × smoking status interaction. Results There was no evidence of association between BMI and genotype in the never smokers {difference per T-allele: 0.05 kg/m2 [95% confidence interval (95% CI): −0.05 to 0.18]; P = 0.25}. However, in ever smokers, each additional smoking-related T-allele was associated with a 0.23 kg/m2 (95% CI: 0.13–0.31) lower BMI (P = 8 × 10−6). The effect size was larger in current [0.33 kg/m2 lower BMI per T-allele (95% CI: 0.18–0.48); P = 6 × 10−5], than in former smokers [0.16 kg/m2 (95% CI: 0.03–0.29); P = 0.01]. There was strong evidence of genotype × smoking interaction (P = 0.0001). Conclusions Smoking status modifies the association between the 15q25 variant and BMI, which strengthens evidence that smoking exposure is causally associated with reduced BMI. Smoking cessation initiatives might be more successful if they include support to maintain a healthy BMI.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
DOI：
10.1073/pnas.88.16.7276
发表时间：
1991-08-01
影响因子：
11.1
作者：
HOLLAND, PM;ABRAMSON, RD;GELFAND, DH
通讯作者：
GELFAND, DH
COLAUS研究：一项基于人群的研究，旨在研究心血管危险因素和代谢综合征的流行病学和遗传决定因素。
影响因子：
2.1
作者：
Firmann, Mathieu;Mayor, Vladimir;Vidal, Pedro Marques;Bochud, Murielle;Pecoud, Alain;Hayoz, Daniel;Paccaud, Fred;Preisig, Martin;Song, Kijoung S.;Yuan, Xin;Danoff, Theodore M.;Stirnadel, Heide A.;Waterworth, Dawn;Mooser, Vincent;Waeber, Gerard;Vollenweider, Peter
通讯作者：
Vollenweider, Peter
影响因子：
3.7
作者：
Caporaso N;Gu F;Chatterjee N;Sheng-Chih J;Yu K;Yeager M;Chen C;Jacobs K;Wheeler W;Landi MT;Ziegler RG;Hunter DJ;Chanock S;Hankinson S;Kraft P;Bergen AW
通讯作者：
Bergen AW
影响因子：
2.8
作者：
Knight, B;Shields, BM;Hattersley, AT
通讯作者：
Hattersley, AT