Bluher, Andrew E.

Background and Purpose: Family-based methods for estimating heritability cannot discriminate between shared genetic and shared environmental exposures. Recently, methods have been developed for estimating heritability in population samples using genome-wide SNPs. We used the approach developed by Visscher and colleagues to estimate the heritability of ischemic stroke in Caucasian subjects. In addition to evaluating the overall heritability of ischemic stroke, we assessed whether stroke heritability varies by age, gender, and stroke subtype. Methods: Using publicly available software (GCTA and PLINK), we estimated ischemic stroke heritability stratified by age and gender using genome-wide association (GWA) data from three Caucasian ischemic stroke studies: Ischemic Stroke Genetics Study (ISGS), Bio-Repository of DNA in Stroke (BRAINS), and Genetics of Early-Onset Stroke (GEOS). Weighted means of site-specific heritability point estimates were combined according to a standard fixed effects model. Results: Conclusions: A SNP-based approach may be useful in discerning differences in ischemic stroke heritability between different cohorts and subtypes. Overall, our analysis estimated ischemic stroke heritability to be 31% (SE = 7%), with a suggestion of higher heritability for younger cases. Small vessel stroke showed the highest heritability (58 ± 19%), with cardioembolic showing the lowest heritability (16 ± 14%). It should be emphasized that heritability estimates are population-specific and that the method used only reflects the heritability captured by common SNP variants measured in GWA studies, and not phenotypic variability explained by rare variants.

Background and purposeAlthough the genetic contribution to stroke risk is well known, it remains unclear if young‐onset stroke has a stronger genetic contribution than old‐onset stroke. This study aims to compare the heritability of ischaemic stroke risk between young and old, using common genetic variants from whole‐genome array data in population‐based samples.MethodsThis analysis included 4050 ischaemic stroke cases and 5765 controls from six study populations of European ancestry; 47% of cases were young‐onset stroke (age < 55 years). To quantify the heritability for stroke risk in these unrelated individuals, the pairwise genetic relatedness was estimated between individuals based on their whole‐genome array data using a mixed linear model. Heritability was estimated separately for young‐onset stroke and old‐onset stroke (age ≥ 55 years).ResultsHeritabilities for young‐onset stroke and old‐onset stroke were estimated at 42% (±8%, P < 0.001) and 34% (±10%, P < 0.001), respectively.ConclusionsOur data suggest that the genetic contribution to the risk of stroke may be higher in young‐onset ischaemic stroke, although the difference was not statistically significant.