Advances in Stroke
The field of stroke genetics continues to make substantive advances. Large-scale partnerships have led to meta-analyses in ischemic and hemorrhagic stroke, which are yielding reproducible genetic risk factors. Most ischemic stroke risk factors seem to be specific to type, for example, large-vessel stroke. Progress is being made in understanding the pathophysiology of single-gene stroke syndromes. Genetics is also being used to potentially advance pharmacotherapeutics.
In the genome-wide association study (GWAS) era, several themes are emerging. First, heritability seems to vary by ischemic stroke subtype. Using complex trait analysis on a GWAS data set of >3000 individuals, Bevan et al1 found a 37.9% heritability for ischemic stroke overall, but the heritability varied widely by subtype from a high of 40.3% for large-vessel stroke to a low of 16.1% for small-vessel stroke.1 Second, genetic risk factors seem to be subtype-selective. Third, GWAS have yielded more reliable discoveries than candidate gene studies uninformed by GWAS. In the previously cited study by Bevan,1 no candidate gene previously reported as associated with ischemic stroke could be replicated using GWAS data, but 3 loci from related cardiovascular GWAS were significant even after rigorous correction for multiple comparisons.
In the area of ischemic stroke genetics, a partnership between the International Stroke Genetics Consortium and the Wellcome Trust Case Control Consortium 2, which included GWAS data from 5859 cases and 6281 controls, replicated associations …