Heavier smoking may lead to a relative increase in waist circumference : evidence for causal relationship from a Mendelian iandomisation meta-analysis. The CARTA consortium

Objectives: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity. Design: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes. Participants: 148 731 current, former and neversmokers of European ancestry aged >= 16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). Primary outcome measures: Waist and hip circumferences, and waist-hip ratio. Results: The data included up to 66 809 never-smokers, 43 009 former smokers and 38 913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by -0.40% (95% Cl -0.57% to - 0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% Cl - 0.42% to -0.19), -0.08% (-0.19% to 0.03%) and - 0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele. Conclusions: For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity.Peer reviewe

Stratification by Smoking Status Reveals an Association of CHRNA5-A3-B4 Genotype with Body Mass Index in Never Smokers

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