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The effect of body mass index on smoking behaviour and nicotine metabolism: a Mendelian randomization study

Amy Taylor, Rebecca Richmond, Teemu Palviainen, Anu Loukula, Jaakko Kaprio, Caroline Relton, George Davey Smith, Marcus Munafo
doi: https://doi.org/10.1101/299834
Amy Taylor
University of Bristol;
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Rebecca Richmond
University of Bristol;
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Teemu Palviainen
University of Helsinki
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Anu Loukula
University of Helsinki
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Jaakko Kaprio
University of Helsinki
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Caroline Relton
University of Bristol;
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George Davey Smith
University of Bristol;
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Marcus Munafo
University of Bristol;
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  • For correspondence: marcus.munafo@bristol.ac.uk
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Abstract

Background 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. Methods and Findings We undertook Mendelian randomization analyses using 97 genetic variants associated with BMI. We performed two sample Mendelian randomization analyses of the effects of BMI on smoking behaviour in UK Biobank (N=335,921) and the Tobacco and Genetics consortium genomewide association study (GWAS) (N≤74,035) respectively, and two sample Mendelian randomization analyses of the effects of BMI on cotinine levels (N≤4,548) and nicotine metabolite ratio (N≤1,518) in published GWAS, and smoking-related DNA methylation in the Avon Longitudinal Study of Parents and Children (N≤846). In inverse variance weighted Mendelian randomization analysis, there was evidence that higher BMI was causally associated with smoking initiation (OR for ever vs never smoking per one SD increase in BMI: 1.19, 95% CI: 1.11 to 1.27) and smoking heaviness (1.45 additional cigarettes smoked per day per SD increase in BMI, 95% CI: 1.03 to 1.86), but little evidence for a causal effect with smoking cessation. Results were broadly similar using pleiotropy robust methods (MR-Egger, median and weighted mode regression). These results were supported by evidence for a causal effect of BMI on DNA methylation at the aryl-hydrocarbon receptor repressor (AHRR) locus. There was no strong evidence that BMI was causally associated with cotinine, but suggestive evidence for a causal negative association with the nicotine metabolite ratio. Conclusions There is a causal bidirectional association between BMI and smoking, but the relationship is likely to be complex due to opposing effects on behaviour and metabolism. It may be useful to consider BMI and smoking together when designing prevention strategies to minimise the effects of these risk factors on health outcomes.

Copyright 
The copyright holder for this preprint is the author/funder. It is made available under a CC-BY 4.0 International license.
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  • Posted April 16, 2018.

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The effect of body mass index on smoking behaviour and nicotine metabolism: a Mendelian randomization study
Amy Taylor, Rebecca Richmond, Teemu Palviainen, Anu Loukula, Jaakko Kaprio, Caroline Relton, George Davey Smith, Marcus Munafo
bioRxiv 299834; doi: https://doi.org/10.1101/299834
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The effect of body mass index on smoking behaviour and nicotine metabolism: a Mendelian randomization study
Amy Taylor, Rebecca Richmond, Teemu Palviainen, Anu Loukula, Jaakko Kaprio, Caroline Relton, George Davey Smith, Marcus Munafo
bioRxiv 299834; doi: https://doi.org/10.1101/299834

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