Genetics Studies in Ischaemic Stroke

Conventional risk factors such as high blood pressure account for a significant proportion of stroke risk, but much stroke risk remains unexplained. Epidemiological evidence suggests genetic predisposition accounts for some of this unexplained risk. Many candidate genes association studies have been performed but have lead to largely disappointing results. The genome-wide association study (GWAS) approach allows novel associations to be identified with as many as one million polymorphisms (genetic variants) across the genome. It has been successfully applied to other complex diseases, including other cardiovascular diseases, but stroke has lagged behind. A number of GWAS projects in stroke are now underway. Genetic variants originally identified using the GWAS approach in atrial fibrillation and coronary artery disease have been shown to also confer an increased risk of stroke. These associations have been with specific subtypes of stroke, emphasising the importance of accurate stroke subtyping. The use of intermediate phenotypes for stroke, such as white matter hyperintensities on MRI and carotid intima-media thickness, is also discussed.