Ischemic Stroke
ICD-11: 8B11
Disease Overview
Ischemic stroke results from occlusion of cerebral arteries, causing focal brain ischemia and infarction. Etiologic subtypes include large-artery atherosclerosis, cardioembolism, small-vessel disease, and other causes. Heritability ~30–40%; SNP-based h² ~0.12. Key loci include PITX2 (atrial fibrillation), HDAC9 (large-vessel), and genes in blood pressure and lipid pathways. Hypertension, smoking, diabetes, and obesity are major modifiable risk factors; they interact with genetic susceptibility.
Rare in adolescence; risk factors (hypertension, obesity, smoking) established in youth influence lifetime risk.
Genetic Architecture Summary
| Gene | Variant | GWAS p | Evidence | Strength |
|---|---|---|---|---|
| PITX2 | rs2200733 | 1.0e-60 | Atrial fibrillation; cardioembolic stroke | 0.88 |
| HDAC9 | rs11984041 | 1.0e-15 | Large-vessel atherosclerotic stroke | 0.75 |
Heritability
h² SNP: 0.12 — MEGASTROKE consortium (2018)
PRS notes: Stroke PRS adds to clinical risk factors; subtype-specific PRS under development.
Exposure Modifier Panel
| Exposure | Direction | Strength | Confidence | Mechanism hypothesis |
|---|---|---|---|---|
| tobacco | amplify | 0.85 | HIGH | — |
| diet-quality | buffer | 0.6 | MEDIUM | — |
| air-pollution | amplify | 0.55 | MEDIUM | — |
Population Equity Notes
GWAS ancestry breakdown: MEGASTROKE included multi-ancestry; European-weighted.
Transferability notes: Subtype-specific loci replicate with variation; PRS transferability limited.
Data gaps: Diverse stroke GWAS; G×E for modifiable risk factors.
Tissue Context
Visualizations
Risk Shift by Exposure Stratum
Population-level data only — does not predict individual risk
Tissue Relevance
References
- 1.Malik R, et al. (2018). Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke. Nature. doi:10.1038/s41586-018-0178-3
- 2.O'Donnell MJ, et al. (2016). Modifiable risk factors, cardiovascular disease, and stroke. Lancet. doi:10.1016/S0140-6736(16)30169-6