Identifying the Genetic Contribution to Ischemic Stroke

See related article, pages 2726–2732.Ischemic stroke is a multifactorial disease. Its etiology is diverse, and the underlying processes are complex. Besides potentially modifiable risk factors, such as hypertension and smoking, there is evidence of heritability of ischemic stroke. Whereas epidemiologic data estimate that ≈70% of strokes can potentially be prevented by lifestyle modification,1 the role of genetic factors is less clear. Apart from the few single-gene disorders like CADASIL or Fabry disease, no single locus has yet been identified to show a consistent and robust association with multifactorial ischemic stroke. The initial expectancy to find 1 or a few common mutations that substantially contribute to the risk of ischemic stroke shifted toward the hypothesis of a large number of small-effect genetic variants with complex gene-gene and gene-environment interactions. Corresponding to this shift in hypotheses, the prevailing genetic methods applied in the last 2 decades changed …