Role of obesity in smoking behaviour:Mendelian randomisation study in UK Biobank

Objective: To determine whether body mass index (BMI), body fat percentage and waist circumference influence smoking behaviour.Design: The association between genetic variants robustly associated with BMI, body fat percentage and waist circumference were evaluated in relation to three measures of smoking status and intensity in a Mendelian randomization framework. Setting: The main analysis was based on UK Biobank with replication of results in the Tobacco and Genetics (TAG) consortium.Participants: European descent participants from UK Biobank (n=375,434) and the TAG consortium (n=74,035).Main outcome measures: Risk of current and past smoking; number of cigarettes smoked per day; age of smoking initiation.Results: The Mendelian randomization (MR) analysis indicated that each standard deviation increment in BMI (4.6 kg/m2) increased the risk of being a smoker (odds ratio 1.18, 95% confidence interval 1.13 to 1.23, P= 3x10-14). This association was replicated in the TAG consortium data (1.19, 1.06 to 1.33, P= 4x10-3). Further, each standard deviation increment in BMI was estimated to increase smoking intensity by 0.88 cigarettes per day (0.50 to 1.26, P= 5x10-6) in UK Biobank and 1.27 cigarettes per day in the TAG consortium (0.46 to 2.07, P= 2.1x10-3). Similar results were also seen for body fat percentage and waist circumference in both UK Biobank and the TAG consortium data. Conclusions: These results strongly suggest that higher adiposity influences smoking behavior and may have implications for the implementation of public health interventions aiming to reduce the prevalence of these important risk factors