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

doi:10.1371/journal.pbio.3000973

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

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Abstract

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 language	English
Article number	e3000973
Number of pages	13
Journal	PLoS Biology
Volume	18
Issue number	11
DOIs	https://doi.org/10.1371/journal.pbio.3000973
Publication status	Published - 30 Nov 2020

Keywords

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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IEU: MRC Integrative Epidemiology Unit Quinquennial renewal
Gaunt, L. F. (Principal Investigator) & Davey Smith, G. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research

Genome-wide association study of lifetime smoking index in a sample of 462,690 individuals from the UK Biobank
Munafo, M. (Creator), Wootton, R. E. (Creator), Richmond, R. (Contributor), Stujifzand, B. (Contributor), Lawn, R. (Contributor), Sallis, H. M. (Contributor), Taylor, G. M. J. (Contributor), Hemani, G. (Contributor), Jones, H. J. (Contributor), Zammit, S. (Contributor) & Davey Smith, G. (Contributor), University of Bristol, 3 Oct 2019
DOI: 10.5523/bris.10i96zb8gm0j81yz0q6ztei23d, http://data.bris.ac.uk/data/dataset/10i96zb8gm0j81yz0q6ztei23d
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@article{79cd7a536a8942a1adb95d2184b8ca7a,

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

abstract = "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.",

keywords = "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",

author = "Mitchell, {Ruth E} and Kirsty Bates and Wootton, {Robyn E} and Adil Harroud and Richards, {J Brent} and {Davey Smith}, George and Munaf{\`o}, {Marcus R}",

year = "2020",

month = nov,

day = "30",

doi = "10.1371/journal.pbio.3000973",

language = "English",

volume = "18",

journal = "PLoS Biology",

issn = "1544-9173",

publisher = "Public Library of Science",

number = "11",

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TY - JOUR

T1 - Little evidence for an effect of smoking on multiple sclerosis risk

T2 - A Mendelian Randomization study

AU - Mitchell, Ruth E

AU - Bates, Kirsty

AU - Wootton, Robyn E

AU - Harroud, Adil

AU - Richards, J Brent

AU - Davey Smith, George

AU - Munafò, Marcus R

PY - 2020/11/30

Y1 - 2020/11/30

N2 - 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.

AB - 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.

KW - Cigarette Smoking/adverse effects

KW - Disease Susceptibility

KW - Female

KW - Genetic Variation

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Mendelian Randomization Analysis

KW - Multiple Sclerosis/etiology

KW - Odds Ratio

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

U2 - 10.1371/journal.pbio.3000973

DO - 10.1371/journal.pbio.3000973

M3 - Article (Academic Journal)

C2 - 33253141

SN - 1544-9173

VL - 18

JO - PLoS Biology

JF - PLoS Biology

IS - 11

M1 - e3000973

ER -

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

Abstract

Keywords

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Projects

IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

Datasets

Genome-wide association study of lifetime smoking index in a sample of 462,690 individuals from the UK Biobank

Cite this