Abstract
Modifiable risk factors like obesity, hypertension, smoking, physical inactivity or atrial fibrillation account for a significant proportion of the risk for ischaemic stroke, but genetic variation is also believed to contribute to the risk, although few genetic risk variants were identified to date. Common clinical subtypes of stroke are caused by cardiac embolism, large artery atherosclerosis and small cerebral vessel disease. Each of these underlying pathologies may have a specific genetic architecture.Previous genome-wide association studies (GWAS) showed association of variants near PITX2 and ZFHX3 with atrial fibrillation and stroke. ANRIL (antisense Non-coding RNA in the INK4 Locus (harboring the CDKN2A/B genes)) variants were related to a variety of vascular diseases (myocardial infarction, aortic and intracranial aneurysm), including ischaemic stroke. Now a recent GWAS published in Nature Genetics confirmed these previous associations, analyzed the specificity of the previous associations with particular stroke subtypes and identified a new association between HDAC9 and large vessel stroke. The findings suggest that well-recognized clinical stroke subtypes correspond to distinct aetiological entities. However, the molecular pathways that are affected by the identified genetic variants are not yet pinpointed, and the observed associations apply only for some, but not all victims of a specific stroke aetiology.
Highlights
The International Stroke Genetics Consortium and the Wellcome Trust Case Control Consortium 2 published the largest genome-wide association study (GWAS) for ischaemic stroke carried out to date [1]
Five stroke subtypes were defined according to the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification [4], using clinical and diagnostic features: 1) large-artery atherosclerosis, 2) cardioembolism (CE), 3) small-vessel occlusion, 4) stroke of other determined etiology
The currently published genome-wide association studies (GWAS) is a milestone in stroke genetics for several reasons: it demonstrates the power of very large multicenter study samples, advocates the study of distinct stroke subtypes, replicates findings of previous stroke GWAS and identifies a new associated genetic variant
Summary
The International Stroke Genetics Consortium and the Wellcome Trust Case Control Consortium 2 published the largest genome-wide association study (GWAS) for ischaemic stroke carried out to date [1]. Background The International Stroke Genetics Consortium and the Wellcome Trust Case Control Consortium 2 published the largest genome-wide association study (GWAS) for ischaemic stroke carried out to date [1]. * Correspondence: Caspar.Grond-Ginsbach@med.uni-heidelberg.de 2Department of Neurology, University of Heidelberg, D-69120 Heidelberg, Germany Full list of author information is available at the end of the article causes such as arterial dissection, inherited diseases of the coagulation system or vasculitis), and 5) stroke of undetermined etiology.
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