A balloon-like weak spot in a brain artery wall, affecting about 2% of people — three studies from 2008 to 2012 found 6 contributing variants, on this page, including one confirmed twice independently.
Solid lines are connections this site curates. Dashed lines mean the two ends share a research paper — worth knowing, and not a claim that one explains the other.
An intracranial aneurysm is a balloon-like dilation in the wall of an artery inside the skull. Most cause no symptoms, but rupture leads to hemorrhagic stroke — one of the world's most serious, often fatal or severely disabling events. The condition affects roughly 2% of the population and accounts for an estimated 500,000 hemorrhagic strokes a year worldwide, typically striking in mid-life around age 50.
A 2008 study of Finnish, Dutch, and Japanese cohorts — more than 2,100 cases and 8,000 controls — found a risk locus near SOX17, a gene required for endothelial cells (the cells lining blood vessels) to form and be maintained. This page's rs10958409 is that original 2008 finding. A larger 2010 study, combining Europe and Japan into 5,891 cases and 14,181 controls, independently confirmed the SOX17 signal (this page's second SOX17 variant, rs9298506) and found three further new loci: RBBP8 (rs11661542), STARD13 (rs9315204), and a gene-rich region at chromosome 10q24.32 containing CNNM2 (rs12413409). That 2010 study noted several of these genes play a role in cell-cycle progression — plausibly affecting the vascular progenitor cells responsible for forming and repairing blood vessels.
A separate 2012 study in a Japanese population (1,383 plus 1,048 cases across two stages, against 5,484 plus 7,212 controls) found a variant near EDNRA (rs6842241), on this page. The same study ran a functional follow-up and found that two alleles of a nearby variant bind differently to a nuclear protein and drive different levels of gene activity — direct evidence, beyond statistical association, that this locus likely changes how much EDNRA protein gets made. EDNRA also appears on this site's peripheral artery disease page.
2026-05-27 · Genome-Wide Association Study and Fine Mapping Uncover Key Genetic Loci and Credible Genes of Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage. Stroke. 2026. DOI:10.1161/strokeaha.126.055253
Fine-mapping brain aneurysm genetics turns up JAK inhibitors as an unexpected drug-repurposing lead
Intracranial aneurysm (IA) rupture causes aneurysmal subarachnoid hemorrhage, a highly lethal event with no effective preventative drug therapy. This multiancestry study across European and East Asian cohorts found 3 novel IA-associated loci and, integrating six different analytical methods (functional annotation, polygenic priority scoring, transcriptome-wide association, Mendelian randomization and more), prioritized a credible set of 40 candidate genes -- with GPX1 and NPC1 among the top-ranked. An expression-based classifier distinguished IA cases from controls with strong accuracy (AUC 0.89), and a polygenic score evaluated in UK Biobank reached AUC 0.83, though the authors caution this needs validation in further independent cohorts before any clinical use. The study also found a nominal interaction between genetic risk and smoking, a known modifiable IA risk factor. Its computational drug-repurposing analysis nominated 32 drug classes as hypothesis-generating candidates, including JAK inhibitors and dopamine receptor antagonists -- unexpected connections given neither class is currently used for aneurysm prevention, and the authors are explicit these are leads for future experimental testing, not established treatments. This site's intracranial aneurysm page carries 6 variants; GPX1 and NPC1 are not currently among them.
2025-10-01 · Genome-wide Association Studies of over 30,000 Samples with Bone Mineral Density at Multiple Skeletal Sites and Its Clinical Relevance. Genomics, Proteomics & Bioinformatics. 2025. DOI:10.1093/gpbjnl/qzaf097
Bone density at the skull, unexpectedly, is genetically linked to brain aneurysm risk
This study explicitly set out to move GWAS findings toward clinical use, analyzing DXA-derived bone mineral density (BMD) at 11 skeletal sites in over 30,000 UK Biobank Europeans. It found 91 independent loci across the BMD traits and fracture risk, including 5 genuinely novel ones (ABCA1, CHSY1, CYP24A1, SWAP70, PAX1), each replicating independently in both men and women. Polygenic risk scores for BMD were independently associated with fracture risk, though combining them with the clinical FRAX fracture-risk tool only modestly improved prediction beyond FRAX alone -- an honestly reported limited clinical gain, not a breakthrough. The more unexpected finding was a genetic correlation and shared polygenicity between head-specific BMD and intracranial aneurysm (IA) risk -- these are not obviously related conditions, and this represents a genuine biological link this site's intracranial aneurysm page (which already carries a different 2026 finding) did not previously document. Integrating gene expression data, the study prioritized ESR1 and SREBF1 as druggable targets, and specifically flagged omega-3 polyunsaturated fatty acid (PUFA) supplements -- already widely available, not a new drug -- as a repurposing candidate for osteoporosis prevention worth investigating. This site's heel bone mineral density page carries 459 variants; ABCA1, CHSY1, CYP24A1, SWAP70 and PAX1 are not currently among them.
Intracranial aneurysms are detected by brain imaging (CT, MRI, or angiography), not by any variant on this page. The variants here describe genetic contributors to overall population risk found in large research studies — none is used clinically to decide who needs screening or how an aneurysm should be treated.
Anyone with a strong family history of intracranial aneurysm or a known connective-tissue or vascular condition should discuss personal screening with a doctor — a decision based on family and medical history, not on any variant listed here.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Intracranial Aneurysm comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 6 of 7 linked studies with a resolved discovery ancestry.
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Intracranial Aneurysm. MyGeneLog™. https://www.mygenelog.com/conditions/intracranial-aneurysm
A balloon-like dilation in the wall of an artery inside the skull. Most cause no symptoms, but rupture leads to hemorrhagic stroke. It affects roughly 2% of the population.
The SOX17 locus was found independently by two separate studies, in 2008 and again in 2010 — this page carries a variant from each. The EDNRA variant is unusual in having direct functional evidence (not just statistical association) that it changes gene activity.
No. Intracranial aneurysms are detected by brain imaging, not genotype. These variants describe population-level risk contributors found in research studies.
No single variant here is used clinically to decide on screening. Anyone with a strong family history of intracranial aneurysm should discuss personal screening with a doctor.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.