Evidence map›Paper›PMID 23733552›Full record

SynthesisNeurology2013

Genetic risk factors for intracranial aneurysms: a meta-analysis in more than 116,000 individuals.

Varinder S Alg, Reecha Sofat, Henry Houlden, David J Werring

Abstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

81 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Gene therapy for intracranial aneurysms: systemic review.Journal of neurointerventional surgery · 2025
    Pooled it
  2. Genetic susceptibility to cerebrovascular disease: A systematic review.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018
    Pooled it
  3. Pooled it
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
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  11. Biology, Physics, and Genetics of Intracranial Aneurysm Formation: A Review.Journal of neurological surgery. Part A, Central European neurosurgery · 2026
    Review
  12. Article
  13. Article
  14. Review
  15. Molecular Targets for Intracranial Aneurysm Treatment.International journal of molecular sciences · 2025
    Review
  16. Bioinformatics analysis reveals major hub genes involved with extracellular matrix and inflammatory and endocrine pathways associated with intracranial aneurysm tissue.Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences · 2025
    Article
  17. Review
  18. Article
  19. Observational
  20. Review

21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Varinder S AlgDepartment of Brain Repair and Rehabilitation, Institute of Neurology, Centre for Clinical Pharmacology, University College London, London, UK.
Reecha Sofat
Henry Houlden
David J Werring

Funding

Department of HealthMedical Research Council G0802760Medical Research Council G1001253Medical Research Council G108/638Medical Research Council MR/J004758/1
6 · The paper itself

Abstract

objectiveThere is an urgent need to identify risk factors for sporadic intracranial aneurysm (IA) development and rupture. A genetic component has long been recognized, but firm conclusions have been elusive given the generally small sample sizes and lack of replication. Genome-wide association studies have overcome some limitations, but the number of robust genetic risk factors for IA remains uncertain.

methodsWe conducted a comprehensive systematic review and meta-analysis of all genetic association studies (including genome-wide association studies) of sporadic IA, conducted according to Strengthening the Reporting of Genetic Association Studies and Human Genome Epidemiology Network guidelines. We tested the robustness of associations using random-effects and sensitivity analyses.

resultsSixty-one studies including 32,887 IA cases and 83,683 controls were included. We identified 19 single nucleotide polymorphisms associated with IA. The strongest associations, robust to sensitivity analyses for statistical heterogeneity and ethnicity, were found for the following single nucleotide polymorphisms: on chromosome 9 within the cyclin-dependent kinase inhibitor 2B antisense inhibitor gene (rs10757278: odds ratio [OR] 1.29; 95% confidence interval [CI] 1.21-1.38; and rs1333040: OR 1.24; 95% CI 1.20-1.29), on chromosome 8 near the SOX17 transcription regulator gene (rs9298506: OR 1.21; 95% CI 1.15-1.27; and rs10958409: OR 1.19; 95% CI 1.13-1.26), and on chromosome 4 near the endothelin receptor A gene (rs6841581: OR 1.22; 95% CI 1.14-1.31).

conclusionsOur comprehensive meta-analysis confirms a substantial genetic contribution to sporadic IA, implicating multiple pathophysiologic pathways, mainly relating to vascular endothelial maintenance. However, the limited data for IA compared with other complex diseases necessitates large-scale replication studies in a full spectrum of populations, with investigation of how genetic variants relate to phenotype (e.g., IA size, location, and rupture status).

Indexed as

Chromosomes, Human, Pair 4Chromosomes, Human, Pair 8Chromosomes, Human, Pair 9Genome-Wide Association StudyHumansIntracranial AneurysmPolymorphism, Single NucleotideRisk Factors

Identifiers

PMID23733552
PMCPMC3716358

What OpenQuestion holds

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Registered trials

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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.