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Smoking and multiple sclerosis risk: a Mendelian randomization study
BACKGROUND: 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 occurr...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501136/ https://www.ncbi.nlm.nih.gov/pubmed/32529581 http://dx.doi.org/10.1007/s00415-020-09980-4 |
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author | Vandebergh, Marijne Goris, An |
author_facet | Vandebergh, Marijne Goris, An |
author_sort | Vandebergh, Marijne |
collection | PubMed |
description | BACKGROUND: 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. METHODS: 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. RESULTS: 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/m(2) units, confers a 30% increase in MS risk. CONCLUSION: Despite observational studies repeatedly reporting an association between smoking and increased risk for MS, MR analyses on smoking phenotypes and MS risk could not confirm a causal relationship. This is in contrast with BMI, where observational studies and MR agree on a causal contribution. The reasons for the discrepancy between observational studies and our MR study concerning smoking and MS require further investigation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00415-020-09980-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7501136 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-75011362020-10-01 Smoking and multiple sclerosis risk: a Mendelian randomization study Vandebergh, Marijne Goris, An J Neurol Original Communication BACKGROUND: 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. METHODS: 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. RESULTS: 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/m(2) units, confers a 30% increase in MS risk. CONCLUSION: Despite observational studies repeatedly reporting an association between smoking and increased risk for MS, MR analyses on smoking phenotypes and MS risk could not confirm a causal relationship. This is in contrast with BMI, where observational studies and MR agree on a causal contribution. The reasons for the discrepancy between observational studies and our MR study concerning smoking and MS require further investigation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00415-020-09980-4) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-06-11 2020 /pmc/articles/PMC7501136/ /pubmed/32529581 http://dx.doi.org/10.1007/s00415-020-09980-4 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Communication Vandebergh, Marijne Goris, An Smoking and multiple sclerosis risk: a Mendelian randomization study |
title | Smoking and multiple sclerosis risk: a Mendelian randomization study |
title_full | Smoking and multiple sclerosis risk: a Mendelian randomization study |
title_fullStr | Smoking and multiple sclerosis risk: a Mendelian randomization study |
title_full_unstemmed | Smoking and multiple sclerosis risk: a Mendelian randomization study |
title_short | Smoking and multiple sclerosis risk: a Mendelian randomization study |
title_sort | smoking and multiple sclerosis risk: a mendelian randomization study |
topic | Original Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501136/ https://www.ncbi.nlm.nih.gov/pubmed/32529581 http://dx.doi.org/10.1007/s00415-020-09980-4 |
work_keys_str_mv | AT vandeberghmarijne smokingandmultiplesclerosisriskamendelianrandomizationstudy AT gorisan smokingandmultiplesclerosisriskamendelianrandomizationstudy |