Abstract
Given clear evidence that smoking lowers weight, it is possible that individuals with higher body mass index (BMI) smoke in order to lose or maintain their weight. We performed Mendelian randomization (MR) analyses of the effects of BMI on smoking behaviour in UK Biobank and the Tobacco and Genetics Consortium genome-wide association study (GWAS), on cotinine levels and nicotine metabolite ratio (NMR) in published GWAS and on DNA methylation in the Avon Longitudinal Study of Parents and Children. Our results indicate that higher BMI causally influences lifetime smoking, smoking initiation, smoking heaviness and also DNA methylation at the aryl-hydrocarbon receptor repressor (AHRR) locus, but we do not see evidence for an effect on smoking cessation. While there is no strong evidence that BMI causally influences cotinine levels, suggestive evidence for a negative causal influence on NMR may explain this. There is a causal effect of BMI on smoking, but the relationship is likely to be complex due to opposing effects on behaviour and metabolism.
Highlights
Smoking and obesity are amongst the leading preventable causes of mortality and morbidity worldwide [1]
Using genetic variants associated with body mass index (BMI) from the largest published genome-wide association studies (GWAS) of BMI to date [30], we investigated whether BMI causes differences in smoking behaviour and total tobacco exposure by looking at both self-reported measures of smoking and biological measures of exposure
Within UK Biobank, each SD increase in genetic risk score was associated with a 0.64 kg/m2 increase in BMI (95% confidence interval (CI): 0.62–0.65)
Summary
Smoking and obesity are amongst the leading preventable causes of mortality and morbidity worldwide [1]. Human Molecular Genetics, 2019, Vol 28, No 8 1323 diet [4] and the strong links between smoking, obesity and sociodemographic factors [5], establishing the existence of and direction of causality is difficult. There is good evidence from MR studies, using a genetic variant that influences the number of cigarettes consumed per day among smokers, that heavier smoking causes a reduction in BMI and other measures of adiposity [7,8,9]. This may be explained by nicotine increasing metabolic rate and/or lowering appetite and changing energy balance [2]. There is a large body of evidence showing that smoking cessation is accompanied by weight gain [10,11,12,13,14,15], though with large individual variation in the amount gained
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
