Little evidence for an effect of smoking on multiple sclerosis risk: A Mendelian Randomization study

Ruth E Mitchell*, Kirsty Bates, Robyn E Wootton, Adil Harroud, J Brent Richards, George Davey Smith, Marcus R Munafò

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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The causes of multiple sclerosis (MS) remain unknown. Smoking has been associated with MS in observational studies and is often thought of as an environmental risk factor. We used two-sample Mendelian randomization (MR) to examine whether this association is causal using genetic variants identified in genome-wide association studies (GWASs) as associated with smoking. We assessed both smoking initiation and lifetime smoking behaviour (which captures smoking duration, heaviness, and cessation). There was very limited evidence for a meaningful effect of smoking on MS susceptibility as measured using summary statistics from the International Multiple Sclerosis Genetics Consortium (IMSGC) meta-analysis, including 14,802 cases and 26,703 controls. There was no clear evidence for an effect of smoking on the risk of developing MS (smoking initiation: odds ratio [OR] 1.03, 95% confidence interval [CI] 0.92-1.61; lifetime smoking: OR 1.10, 95% CI 0.87-1.40). These findings suggest that smoking does not have a detrimental consequence on MS susceptibility. Further work is needed to determine the causal effect of smoking on MS progression.

Original languageEnglish
Article numbere3000973
Number of pages13
JournalPLoS Biology
Issue number11
Publication statusPublished - 30 Nov 2020


  • Cigarette Smoking/adverse effects
  • Disease Susceptibility
  • Female
  • Genetic Variation
  • Genome-Wide Association Study
  • Humans
  • Male
  • Mendelian Randomization Analysis
  • Multiple Sclerosis/etiology
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Risk Factors

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