ArticleMolecular neurodegeneration2014
Genetic modifiers in carriers of repeat expansions in the C9ORF72 gene.
Article in Molecular neurodegeneration, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
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Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- Survival and Prognostic Factors in C9orf72 Repeat Expansion Carriers: A Systematic Review and Meta-analysis.JAMA neurology · 2020Pooled it
- Updated meta-analysis of the role of APOE ε2/ε3/ε4 alleles in frontotemporal lobar degeneration.Oncotarget · 2017Pooled it
- Longitudinal imaging inNeuroImage. Clinical · 2016Trial
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- Disease-modifying effects of TMEM106B in genetic frontotemporal dementia: a longitudinal GENFI study.Brain : a journal of neurology · 2025Article
- The role of endolysosomal progranulin and TMEM106B in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Proteomics of the temporal cortex in semantic dementia reveals brain-region specific molecular pathology and regulation of the TDP-43-ANXA11 interactome.Acta neuropathologica communications · 2025Article
- Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells.Translational neurodegeneration · 2025Review
- Sod1-deficient cells are impaired in formation of the modified nucleosides mcmRNA (New York, N.Y.) · 2024Article
- Mechanism-free repurposing of drugs for C9orf72-related ALS/FTD using large-scale genomic data.Cell genomics · 2024Article
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- Analytical and clinical validation of a blood progranulin ELISA in frontotemporal dementias.Clinical chemistry and laboratory medicine · 2023Article
- AAV-iScience · 2023Article
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- Association of Copresence of Pathogenic Variants Related to Amyotrophic Lateral Sclerosis and Prognosis.Neurology · 2023Article
- Association of the risk factorFrontiers in aging neuroscience · 2023Article
- The identification of high-performing antibodies for transmembrane protein 106B (TMEM106B) for use in Western blot, immunoprecipitation, and immunofluorescence.F1000Research · 2023Article
- HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS.Acta neuropathologica · 2022Article
Corrections and comments
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Authors and funding
39 authors at 13 institutions in 3 countries.
Funding
Abstract
backgroundHexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9ORF72) are causative for frontotemporal dementia (FTD) and motor neuron disease (MND). Substantial phenotypic heterogeneity has been described in patients with these expansions. We set out to identify genetic modifiers of disease risk, age at onset, and survival after onset that may contribute to this clinical variability.
resultsWe examined a cohort of 330 C9ORF72 expansion carriers and 374 controls. In these individuals, we assessed variants previously implicated in FTD and/or MND; 36 variants were included in our analysis. After adjustment for multiple testing, our analysis revealed three variants significantly associated with age at onset (rs7018487 [UBAP1; p-value = 0.003], rs6052771 [PRNP; p-value = 0.003], and rs7403881 [MT-Ie; p-value = 0.003]), and six variants significantly associated with survival after onset (rs5848 [GRN; p-value = 0.001], rs7403881 [MT-Ie; p-value = 0.001], rs13268953 [ELP3; p-value = 0.003], the epsilon 4 allele [APOE; p-value = 0.004], rs12608932 [UNC13A; p-value = 0.003], and rs1800435 [ALAD; p-value = 0.003]).
conclusionsVariants identified through this study were previously reported to be involved in FTD and/or MND, but we are the first to describe their effects as potential disease modifiers in the presence of a clear pathogenic mutation (i.e. C9ORF72 repeat expansion). Although validation of our findings is necessary, these variants highlight the importance of protein degradation, antioxidant defense and RNA-processing pathways, and additionally, they are promising targets for the development of therapeutic strategies and prognostic tests.
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Registered trials
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