ArticleBrain : a journal of neurology2025
Neurodegenerative disease in C9orf72 repeat expansion carriers: population risk and effect of UNC13A.
Article in Brain : a journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed.
- Presymptomatic Amyotrophic Lateral Sclerosis: From Early Biomarker Detection to Phenoconversion Prediction.Diagnostics (Basel, Switzerland) · 2026Review
- Clinical genome sequencing in neurodegenerative diseases-outcome in the first 500 patients.Human molecular genetics · 2026Article
- Neural Organoid Models as a Platform for Studying Disease Mechanisms in Amyotrophic Lateral Sclerosis.Journal of neurochemistry · 2026Review
- Microglial Dysfunction Induced by C9ORF72 Dipeptide Repeat Proteins: Biomarker and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Single-nucleus multiomic atlas of ALS primary motor cortex nominates neuroprotective WDR49-expressing astrocytes.Research square · 2026Article
- Long-Term Exposure to Ambient Air Pollution and Incident Amyotrophic Lateral Sclerosis: A Prospective Cohort Analysis of the UK Biobank.Neurology · 2026Article
- From Evasion to Collapse: The Kinetic Cascade of TDP-43 and the Failure of Proteostasis.International journal of molecular sciences · 2026Review
- Loss of Y chromosome and its implications in male amyotrophic lateral sclerosis: insights from the UK Biobank.BMC medicine · 2025Article
- Predicting Phenoconversion to Clinically Manifest ALS: Results of a Large-Scale Proteomic Study.medRxiv : the preprint server for health sciences · 2025Article
- Clinical, neuropathological, and biochemical characterization of ALS in a large CHCHD10 R15L family.medRxiv : the preprint server for health sciences · 2025Article
- Exploring rare coding variants in UK biobank: preliminary associations with motor neuron disease.Frontiers in aging neuroscience · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
The C9orf72 hexanucleotide repeat expansion (HRE) is the most common monogenetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Neurodegenerative disease incidence in C9orf72 HRE carriers has been studied using cohorts from disease-affected families or by extrapolating from population disease incidence, potentially introducing bias. Age-specific cumulative incidence of ALS and dementia was estimated using Kaplan-Meier and competing risk models in C9orf72 HRE carriers compared to matched controls in UK Biobank. Risk modification by UNC13A genotype was examined. Of 490 331 individuals with valid genetic data, 701 had >100 repeats in C9orf72 [median age 55 (interquartile range 48-62), follow-up 13.4 years (12.3-14.1)]. The cumulative incidence of ALS or dementia was 66% (95% confidence interval 57%-73%) by age 80 in C9orf72 HRE carriers versus 5.8% (4.5%-7.0%) in controls, or 58% (50%-64%) versus 5.1% (4.1%-6.4%), accounting for the competing risk of other-cause mortality. Forty-one per cent of dementia incidence accrued between age 75-80. C-allele homozygosity at rs12608932 in UNC13A increased ALS or dementia risk in C9orf72 HRE carriers [hazard ratio 1.81 (1.18-2.78)]. C9orf72 HRE disease was incompletely penetrant in this population-based cohort, with risk modified by UNC13A genotype. This has implications for counselling at-risk individuals and modelling expected phenoconversion for prevention trials.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.