ArticleFrontiers in cellular neuroscience2022
Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data.
Article in Frontiers in cellular neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 9 citations in OpenAlex.
- Association between leukocyte telomere length and neurodegenerative diseases: a prospective cohort in the UK Biobank.Journal of neurology · 2026Article
- Dissecting epigenetic age acceleration in amyotrophic lateral sclerosis.Epigenomics · 2025Article
- Molecular hallmarks of ageing in amyotrophic lateral sclerosis.Cellular and molecular life sciences : CMLS · 2024Review
- Unsupervised machine learning identifies distinct ALS molecular subtypes in post-mortem motor cortex and blood expression data.Acta neuropathologica communications · 2023Article
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45 authors at 20 institutions in 13 countries.
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Abstract
Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to progressive weakness of voluntary muscles, with death following from neuromuscular respiratory failure, typically within 3 to 5 years. There is a strong genetic contribution to ALS risk. In 10% or more, a family history of ALS or frontotemporal dementia is obtained, and the Mendelian genes responsible for ALS in such families have now been identified in about 50% of cases. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. Sex and age are risk factors for ALS and we therefore investigated telomere length in ALS. Methods: Samples were from Project MinE, an international ALS whole genome sequencing consortium that includes phenotype data. For validation we used donated brain samples from motor cortex from people with ALS and controls. Ancestry and relatedness were evaluated by principal components analysis and relationship matrices of DNA microarray data. Whole genome sequence data were from Illumina HiSeq platforms and aligned using the Isaac pipeline. TelSeq was used to quantify telomere length using whole genome sequence data. We tested the association of telomere length with ALS and ALS survival using Cox regression. Results: There were 6,580 whole genome sequences, reducing to 6,195 samples (4,315 from people with ALS and 1,880 controls) after quality control, and 159 brain samples (106 ALS, 53 controls). Accounting for age and sex, there was a 20% (95% CI 14%, 25%) increase of telomere length in people with ALS compared to controls (p = 1.1 × 10 Discussion: Although telomeres shorten with age, longer telomeres are a risk factor for ALS and worsen prognosis. Longer telomeres are associated with ALS.
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