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

Hum Mol Genet. 2019 Apr 15;28(8):1322-1330. doi: 10.1093/hmg/ddy434.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Mass Index
  • Body Weight / genetics
  • Cohort Studies
  • DNA Methylation / genetics
  • Female
  • Genome-Wide Association Study / methods
  • Humans
  • Longitudinal Studies
  • Male
  • Mendelian Randomization Analysis / methods
  • Middle Aged
  • Nicotine / genetics
  • Nicotine / metabolism*
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • Smoking / genetics*
  • Smoking / metabolism*
  • Smoking / physiopathology
  • Smoking Cessation

Substances

  • Nicotine