期刊
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
卷 40, 期 6, 页码 1617-1628出版社
OXFORD UNIV PRESS
DOI: 10.1093/ije/dyr077
关键词
Smoking; BMI; SNP; genetic association; interaction
资金
- UK Medical Research Council
- Wellcome Trust [WT084762]
- University of Bristol
- BRHS is a British Heart Foundation research group [RG/08/013/25942]
- British Heart Foundation [FS05/125]
- Department of Health (England)
- British Heart Foundation
- GlaxoSmithKline
- Faculty of Biology and Medicine of Lausanne, Switzerland
- Swiss National Science Foundation [33CSCO-122661, 3200B0-105993, 3200B0-1180308, 33CSC0122661]
- GlaxoSmithKline (Psychiatry Center of Excellence for Drug Discovery and Genetics Division, Drug Discovery-Verona, RD)
- South West NHS Research and Development
- Exeter NHS Research and Development
- Darlington Trust
- Peninsula NIHR Clinical Research Facility at the University of Exeter
- NHS
- Sir Henry Wellcome Postdoctoral Fellowship [085541/Z/08/Z]
- UK Medical Research Council [G0600705]
- British Heart Foundation [RG/08/013/25942] Funding Source: researchfish
- Medical Research Council [G0802736, G0500070, G0600705, G9815508] Funding Source: researchfish
- MRC [G0802736, G0600705, G0500070] Funding Source: UKRI
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 x 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/m(2) [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/m(2) (95% CI: 0.13-0.31) lower BMI (P = 8 x 10(-6)). The effect size was larger in current [0.33 kg/m(2) lower BMI per T-allele (95% CI: 0.18-0.48); P = 6 x 10(-5)], than in former smokers [0.16 kg/m(2) (95% CI: 0.03-0.29); P = 0.01]. There was strong evidence of genotype x 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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