Smoking and multiple sclerosis risk: a Mendelian randomization study.

Journal of Neurology
Marijne Vandebergh, An Goris

Abstract

Striking changes in the demographic pattern of multiple sclerosis (MS) strongly indicate an influence of modifiable exposures, which lend themselves well to intervention. It is important to pinpoint which of the many environmental, lifestyle, and sociodemographic changes that have occurred over the past decades, such as higher smoking and obesity rates, are responsible. Mendelian randomization (MR) is an elegant tool to overcome limitations inherent to observational studies and leverage human genetics to inform prevention strategies in MS. We use genetic variants from the largest genome-wide association study for smoking phenotypes (initiation: N = 378, heaviness: N = 55, lifetime smoking: N = 126) and body mass index (BMI, N = 656) and apply these as instrumental variables in a two-sample MR analysis to the most recent meta-analysis for MS. We adjust for the genetic correlation between smoking and BMI in a multivariable MR. In univariable and multivariable MR, smoking does not have an effect on MS risk nor explains part of the association between BMI and MS risk. In contrast, in both analyses each standard deviation increase in BMI, corresponding to roughly 5 kg/m2 units, confers a 30% increase in MS risk. Despite observationa...Continue Reading

References

Sep 26, 1992·BMJ : British Medical Journal·G D Smith, A N Phillips
Mar 11, 2005·Brain : a Journal of Neurology·Miguel A HernánHershel Jick
Sep 22, 2007·Statistics in Medicine·Debbie A LawlorGeorge Davey Smith
Oct 31, 2008·Lancet·Alastair Compston, Alasdair Coles
Apr 20, 2010·Lancet Neurology·Nils Koch-Henriksen, Per Soelberg Sørensen
Jan 21, 2011·PloS One·Adam E HandelSreeram V Ramagopalan
Aug 13, 2011·Nature·UNKNOWN International Multiple Sclerosis Genetics ConsortiumAlastair Compston
Oct 1, 2013·Nature Genetics·UNKNOWN International Multiple Sclerosis Genetics Consortium (IMSGC)Jacob L McCauley
Oct 12, 2013·Genetic Epidemiology·Stephen BurgessSimon G Thompson
Oct 23, 2013·European Journal of Epidemiology·Anna Karin HedströmLars Alfredsson
May 8, 2015·Multiple Sclerosis : Clinical and Laboratory Research·Kelly HilvenAn Goris
Jun 8, 2015·International Journal of Epidemiology·Jack BowdenStephen Burgess
Aug 26, 2015·PLoS Medicine·Lauren E MokryJ Brent Richards
Sep 8, 2015·Nature Genetics·Loukas MoutsianasGil McVean
Mar 11, 2016·The American Journal of Clinical Nutrition·Philip C HaycockGeorge Davey Smith
Jun 29, 2016·PLoS Medicine·Lauren E MokryJ Brent Richards
Sep 22, 2016·Neurology. Genetics·Brooke RheadLisa F Barcellos
Dec 10, 2016·Nature Reviews. Neurology·Tomas OlssonLars Alfredsson
Mar 31, 2017·Neurology·Milena A GianfrancescoUNKNOWN Network of Pediatric Multiple Sclerosis Centers
May 21, 2017·European Journal of Epidemiology·Stephen Burgess, Simon G Thompson
Oct 19, 2017·International Journal of Epidemiology·Fernando Pires HartwigJack Bowden
Oct 23, 2017·Multiple Sclerosis and Related Disorders·Michelle L Degelman, Katya M Herman
Jan 6, 2018·Multiple Sclerosis : Clinical and Laboratory Research·Kelly HilvenBénédicte Dubois
Oct 23, 2018·Cell·UNKNOWN International Multiple Sclerosis Genetics Consortium. Electronic address: chris.cotsapas@yale.edu, UNKNOWN International Multiple Sclerosis Genetics Consortium
Jan 20, 2019·Nature Communications·Simon HaworthNicholas J Timpson
Feb 21, 2019·Annals of Neurology·Yiqiang Zhan, Fang Fang
Jun 27, 2019·Annals of Neurology·Susanna C LarssonKarl Michaëlsson
Aug 2, 2019·International Journal of Epidemiology·Jessica M B ReesStephen Burgess
Oct 12, 2019·Science·UNKNOWN International Multiple Sclerosis Genetics Consortium
Apr 18, 2020·European Heart Journal·Susanna C LarssonStephen Burgess

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Citations

Sep 9, 2021·Expert Review of Neurotherapeutics·Amin ZarghamiBruce V Taylor
Jan 14, 2022·Seminars in Immunopathology·Woori Kim, Nikolaos A Patsopoulos

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Software Mentioned

TwoSampleMR
R
GIANT
LDlinkR

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