SynthesisNeurology2015
Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease.
Synthesis in Neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 3 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
78 citing papers in PubMed, 3 syntheses or guidelines pooled it, 130 citations in OpenAlex.
- Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities.Stroke · 2020Pooled it
- Pooled it
- Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke.Neurology · 2016Pooled it
- Whole-Exome Sequencing in 22 Young Ischemic Stroke Patients With Familial Clustering of Stroke.Stroke · 2020Trial
- Biomarker advancements in cerebral small vessel disease: An overview.Neural regeneration research · 2026Article
- Stratification of Phenotypes in Childhood-OnsetNeurology. Genetics · 2026Article
- Collagen IV in Gould syndrome and Alport syndrome.Nature reviews. Nephrology · 2025Review
- Genetic and epigenetic architectures of stroke: Insights from GWAS to precision medicine.Neurochemistry international · 2025Review
- Pediatric pulmonary hemorrhage observed in non-vascular and vascular Ehlers-Danlos syndrome.Orphanet journal of rare diseases · 2025Article
- Prognostic significance and multivariate modeling of COL4A family genes and HMGA2 in glioma.Frontiers in pharmacology · 2025Article
- Association of the COL4A2 Gene Polymorphisms with Primary Intracerebral Hemorrhage Risk and Outcome in Chinese Han Population.Molecular neurobiology · 2024Article
- Identification of a novel intronic variant in COL4A2 gene associated with fetal severe cerebral encephalomalacia and subdural hemorrhage.BMC medical genomics · 2024Article
- Collagen IV deficiency causes hypertrophic remodeling and endothelium-dependent hyperpolarization in small vessel disease with intracerebral hemorrhage.EBioMedicine · 2024Article
- Pathophysiology of cerebral small vessel disease: a journey through recent discoveries.The Journal of clinical investigation · 2024Review
- A novel human iPSC model of COL4A1/A2 small vessel disease unveils a key pathogenic role of matrix metalloproteinases.Stem cell reports · 2023Article
- Pontine autosomal dominant microangiopathy with leukoencephalopathy: Col4A1 gene variants in the original family and sporadic stroke.Journal of neurology · 2023Article
- Arteriolar neuropathology in cerebral microvascular disease.Neuropathology and applied neurobiology · 2023Review
- GWAS on retinal vasculometry phenotypes.PLoS genetics · 2023Article
- Elevated TGFβ signaling contributes to cerebral small vessel disease in mouse models of Gould syndrome.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Genetic considerations in cerebral small vessel diseases.Frontiers in neurology · 2023Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
57 authors at 1 institution in 1 country.
Funding
Abstract
objectivesWe hypothesized that common variants in the collagen genes COL4A1/COL4A2 are associated with sporadic forms of cerebral small vessel disease.
methodsWe conducted meta-analyses of existing genotype data among individuals of European ancestry to determine associations of 1,070 common single nucleotide polymorphisms (SNPs) in the COL4A1/COL4A2 genomic region with the following: intracerebral hemorrhage and its subtypes (deep, lobar) (1,545 cases, 1,485 controls); ischemic stroke and its subtypes (cardioembolic, large vessel disease, lacunar) (12,389 cases, 62,004 controls); and white matter hyperintensities (2,733 individuals with ischemic stroke and 9,361 from population-based cohorts with brain MRI data). We calculated a statistical significance threshold that accounted for multiple testing and linkage disequilibrium between SNPs (p < 0.000084).
resultsThree intronic SNPs in COL4A2 were significantly associated with deep intracerebral hemorrhage (lead SNP odds ratio [OR] 1.29, 95% confidence interval [CI] 1.14-1.46, p = 0.00003; r(2) > 0.9 between SNPs). Although SNPs associated with deep intracerebral hemorrhage did not reach our significance threshold for association with lacunar ischemic stroke (lead SNP OR 1.10, 95% CI 1.03-1.18, p = 0.0073), and with white matter hyperintensity volume in symptomatic ischemic stroke patients (lead SNP OR 1.07, 95% CI 1.01-1.13, p = 0.016), the direction of association was the same. There was no convincing evidence of association with white matter hyperintensities in population-based studies or with non-small vessel disease cerebrovascular phenotypes.
conclusionsOur results indicate an association between common variation in the COL4A2 gene and symptomatic small vessel disease, particularly deep intracerebral hemorrhage. These findings merit replication studies, including in ethnic groups of non-European ancestry.
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.