Associations between lifestyle and amyotrophic lateral sclerosis stratified by C9orf72 genotype: a longitudinal, population-based, case-control study
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Background Amyotrophic lateral sclerosis (ALS) is considered to be caused by both genetic and environmental factors. The causal cascade is, however, not known. We aimed to assess lifestyle during the presymptomatic phase of ALS, stratified by C9orf72 mutation, and examine evidence supporting causality of lifestyle factors. Methods This study was a longitudinal, population-based, case-control study that used data from the Prospective ALS study the Netherlands. We included patients with a C9orf72 mutation (C9+ group), patients without a C9orf72 mutation (C9- group), and controls. Patients fulfilled the revised El Escorial criteria and were recruited through neurologists and rehabilitation physicians in the Netherlands as well as the Dutch Neuromuscular Patient Association and ALS Centrum website. 1322 population-based controls, matched for age and sex, were enrolled via the patients' general practitioners. Blood relatives or spouses of patients were not eligible as controls. We studied the relationship between ALS risk and smoking, alcohol, physical activity, body-mass index (BMI), and energy intake by the use of structured questionnaires. Smoking, physical activity, and BMI were longitudinally assessed up to 50 years before onset (defined as the period before onset of muscle weakness or bulbar symptoms for cases, or age at completing the questionnaire for controls). We calculated posterior probabilities (P(θ|x)) for causal effects of smoking, alcohol, and BMI, using Bayesian i…
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Repeats of 24 or more hexanucleotides in C9orf72 are considered pathogenic, leading to earlier diagnosis of ALS.
“Repeats of 24 or more hexanucleotides are considered pathogenic, leading to earlier diagnosis of ALS [6, 7].”
From Lifestyle and medical conditions in relation to ALS risk and progression—an introduction to the Swedish ALSrisc Study (2024) · cites this paper as [7]
A lower BMI has been associated with a higher risk for ALS.
“A lower BMI has been associated with a higher risk for ALS [7, 11, 21–23].”
From Lifestyle and medical conditions in relation to ALS risk and progression—an introduction to the Swedish ALSrisc Study (2024) · cites this paper as [7]
Some observational studies showed a positive association for current smoking but no association for former smoking with ALS risk.
“Some observational studies showed a positive association for current smoking but no association for former smoking [7, 14, 15], while Mendelian Randomization studies have provided evidence for a causal link between smoking and risk for ALS [49].”
From Lifestyle and medical conditions in relation to ALS risk and progression—an introduction to the Swedish ALSrisc Study (2024) · cites this paper as [7]
Cites
Sterne, J. A. C., White, I. R., Carlin, J. B., Spratt, M., Royston, P., Kenward, M. G., Wood, A. M., & Carpenter, J. R. (2009) · BMJ · doi:10.1136/bmj.b2393 · Cited by 7,299 · see citing works
Smoking and amyotrophic lateral sclerosis: A mendelian randomization study
Zhan, Y., & Fang, F. (2019) · Annals of Neurology · doi:10.1002/ana.25443 · Cited by 56 · see citing works
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Chourpiliadis, C., Seitz, C., Lovik, A., Joyce, E. E., Pan, L., Hu, Y., Kläppe, U., Samuelsson, K., Press, R., Ingre, C., et al. (2024) · Journal of Neurology · doi:10.1007/s00415-024-12496-w · Cited by 10 · see citing works
“Some observational studies showed a positive association for current smoking but no association for former smoking [7, 14, 15], while Mendelian Randomization studies have provided evidence for a causal link between smoking and risk for ALS [49].”
BackgroundInfluentialGamez, J., & Carmona, F. (2021) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2021.117586 · Cited by 10 · see citing works
- Authors
- Westeneng, H.-J., van Veenhuijzen, K., van der Spek, R. A., Peters, S., Visser, A. E., van Rheenen, W., Veldink, J. H., & van den Berg, L. H.
- Affiliations
- Utrecht University (NL)
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 20
- Issue
- 5
- Pages
- 373-384
- ISSN
- 1474-4422 (ISSN-L)
- OpenAlex
- W3153769444
- Cited by
- 58
- References
- 2
- Citations by year
- 2026: 9 · 2025: 2 · 2024: 16 · 2023: 12 · 2022: 13 · 2021: 6
- FWCI
- 5.62
- Type
- journal article
- Language
- en
- Open access
- green
- dspace.library.uu.nl
- Licence
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- ALS Netherlands Foundation
- European Research Council
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Health Sciences › Medicine › Surgery › Cervical and Thoracic Myelopathy
- Keywords
- amyotrophic lateral sclerosis, C9orf72 mutation, lifestyle factors, smoking, alcohol consumption, physical activity, body mass index, energy intake, presymptomatic phase, causal inference, ALS risk, genetic and environmental risk factors, sex differences, smoking cessation, alcohol cessation
- MeSH terms
- C9orf72 Protein, Age Factors, Aged, Amyotrophic Lateral Sclerosis, Energy Intake, Female, Genotype, Humans, Life Style, Longitudinal Studies, Male, Middle Aged, Mutation, Netherlands, Surveys and Questionnaires, Smoking, Exercise, Body Mass Index, Case-Control Studies
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