ArticleBrain : a journal of neurology2014
Modulation of the age at onset in spinocerebellar ataxia by CAG tracts in various genes.
Article in Brain : a journal of neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 4 of them syntheses that pooled it.
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
94 citing papers in PubMed, 4 syntheses or guidelines pooled it, 173 citations in OpenAlex.
- White matter microstructural alterations in Huntington's disease: a systematic review of diffusion imaging findings.Brain imaging and behavior · 2026Pooled it
- Retinoic Acid-Induced 1 Gene and Neuropsychiatric Diseases: A Systematic Review.Expert reviews in molecular medicine · 2025Pooled it
- Epidemiology of Spinocerebellar Ataxias in Europe.Cerebellum (London, England) · 2024Pooled it
- ATXN2 trinucleotide repeat length correlates with risk of ALS.Neurobiology of aging · 2017Pooled it
- Translational Paradox of Triplet Repeat Expansion Disorders: Synthesizing Clinical Trial Failures to Guide Future Therapeutics.Clinical pharmacology and therapeutics · 2026Review
- Review
- Replication analysis of the PRKN V380L (rs1801582) variant in a Japanese cohort of spinocerebellar ataxia type 3.BMC neurology · 2026Article
- Tandem repeats in human brain evolution and disease susceptibility.Molecules and cells · 2026Review
- Predictive models for ataxia progression and conversion in spinocerebellar ataxia type 1 and 3.Brain : a journal of neurology · 2026Article
- Hereditary Ataxias: From Pathogenesis and Clinical Features to Neuroimaging, Fluid, and Digital Biomarkers-A Scoping Review.International journal of molecular sciences · 2026Review
- Huntington disease: somatic expansion, pathobiology and therapeutics.Nature reviews. Neurology · 2026Review
- Pediatric-onset spinocerebellar ataxia type 3 with dualFrontiers in genetics · 2026Article
- Challenges in Polyglutamine Diseases: From Dysfunctional Neuronal Circuitries to Neuron-Specific CAG Repeat Instability.International journal of molecular sciences · 2025Review
- Long-read sequencing identifies ATXN3 repeat expansions, and transcriptomics reveals disease progression biomarkers and druggable targets for spinocerebellar ataxia type 3.BMC neurology · 2025Article
- Influence of ATXN2 intermediate CAG repeats, 9bp duplication and alternative splicing on SCA3 pathogenesis.Acta neuropathologica communications · 2025Article
- The Natural History Study and Biomarker Collection of the Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA).Cerebellum (London, England) · 2025Review
- Movement Disorders in Hereditary Cerebellar Ataxia.Movement disorders clinical practice · 2025Article
- Redefining the Pathogenic CAG Repeat Units Threshold inNeurology. Genetics · 2025Article
- Spinocerebellar Ataxia Type 2: A Review and Personal Perspective.Neurology. Genetics · 2025Review
- Spinocerebellar Ataxias: Phenotypic Spectrum of PolyQ versus Non-Repeat Expansion Forms.Cerebellum (London, England) · 2024Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
- Commented on by
Authors and funding
34 authors at 20 institutions in 12 countries.
Funding
Abstract
Polyglutamine-coding (CAG)n repeat expansions in seven different genes cause spinocerebellar ataxias. Although the size of the expansion is negatively correlated with age at onset, it accounts for only 50-70% of its variability. To find other factors involved in this variability, we performed a regression analysis in 1255 affected individuals with identified expansions (spinocerebellar ataxia types 1, 2, 3, 6 and 7), recruited through the European Consortium on Spinocerebellar Ataxias, to determine whether age at onset is influenced by the size of the normal allele in eight causal (CAG)n-containing genes (ATXN1-3, 6-7, 17, ATN1 and HTT). We confirmed the negative effect of the expanded allele and detected threshold effects reflected by a quadratic association between age at onset and CAG size in spinocerebellar ataxia types 1, 3 and 6. We also evidenced an interaction between the expanded and normal alleles in trans in individuals with spinocerebellar ataxia types 1, 6 and 7. Except for individuals with spinocerebellar ataxia type 1, age at onset was also influenced by other (CAG)n-containing genes: ATXN7 in spinocerebellar ataxia type 2; ATXN2, ATN1 and HTT in spinocerebellar ataxia type 3; ATXN1 and ATXN3 in spinocerebellar ataxia type 6; and ATXN3 and TBP in spinocerebellar ataxia type 7. This suggests that there are biological relationships among these genes. The results were partially replicated in four independent populations representing 460 Caucasians and 216 Asian samples; the differences are possibly explained by ethnic or geographical differences. As the variability in age at onset is not completely explained by the effects of the causative and modifier sister genes, other genetic or environmental factors must also play a role in these diseases.
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.