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The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration
- Source :
- Nature Communications 13(1), 6901 (2022). doi:10.1038/s41467-022-34620-y, Nature Communications
- Publication Year :
- 2022
- Publisher :
- Springer Science and Business Media LLC, 2022.
-
Abstract
- Superoxide dismutase (SOD1) gene variants may cause amyotrophic lateral sclerosis, some of which are associated with a distinct phenotype. Most studies assess limited variants or sample sizes. In this international, retrospective observational study, we compare phenotypic and demographic characteristics between people with SOD1-ALS and people with ALS and no recorded SOD1 variant. We investigate which variants are associated with age at symptom onset and time from onset to death or censoring using Cox proportional-hazards regression. The SOD1-ALS dataset reports age of onset for 1122 and disease duration for 883 people; the comparator population includes 10,214 and 9010 people respectively. Eight variants are associated with younger age of onset and distinct survival trajectories; a further eight associated with younger onset only and one with distinct survival only. Here we show that onset and survival are decoupled in SOD1-ALS. Future research should characterise rarer variants and molecular mechanisms causing the observed variability. Analysis of age of onset and disease duration in a large, international cohort of people with SOD1-ALS shows that there is a distinct phenotype and that onset and progression are decoupled.<br />United Kingdom, Medical Research Council; Economic and Social Research Council; European Community’s Health Seventh Framework Programme; European Research Council (ERC); Horizon 2020; Framework Programme; Programme Grants for Applied Research; Research and Innovation Programme; Avexis/Novartis; United Kingdom Dementia Research Institute; National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London Maudsley Foundation Trust; King’s College London; Motor Neurone Disease Association; ALS Association; Psychiatry Research Trust; Health Holland, Top Sector Life Sciences & Health; ALS Foundation Netherlands
- Subjects :
- General Physics and Astronomy
VARIANTS
epidemiology [Amyotrophic Lateral Sclerosis]
AMYOTROPHIC-LATERAL-SCLEROSIS
General Biochemistry, Genetics and Molecular Biology
Superoxide Dismutase-1
genetics [Superoxide Dismutase]
Humans
Science & Technology
Multidisciplinary
MUTATIONS
Superoxide Dismutase
Phenotype
Mutation
Amyotrophic Lateral Sclerosis
SOD1 protein, human
General Chemistry
GENE
genetics [Superoxide Dismutase-1]
Multidisciplinary Sciences
genetics [Amyotrophic Lateral Sclerosis]
Multidisciplinary sciences
Science and technology
Science & Technology - Other Topics
TRIAL
ddc:500
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....1fcc5e01a6abb5b8caa38d92dbfb6ae0