Heritability of Ischemic Stroke in Relation to Age, Vascular Risk Factors, and Subtypes of Incident Stroke in Population-Based Studies

Background— Appropriate design of molecular genetic studies of ischemic stroke requires an understanding of the genetic epidemiology of stroke. However, there are no published population-based data on heritability of aetiological subtypes of ischemic stroke, confounding by heritability of other vascular risk factors, or the relationship between heritability and age of onset. Methods— We studied family history of stroke (FHx Stroke ) and of myocardial infarction (FHx MI ) in first-degree relatives in 2 population-based studies (Oxford Vascular Study [OXVASC]; Oxfordshire Community Stroke Project [OCSP]). We related FHx Stroke and FHx MI to subtype of ischemic stroke, age, and the presence of vascular risk factors and performed a systematic review of all studies of FHx Stroke by stroke subtype. Results— In our population-based studies and in 3 hospital-based studies, FHx Stroke was least frequent in cardioembolic stroke (OR=0.74, 95%CI=0.58 to 0.95, P =0.02) but was equally frequent in the other subtypes. In OXVASC and OCSP, FHx Stroke ( P =0.02), FHx MI ( P =0.04), and FHx of either ( P =0.006) were associated with stroke at a younger age. Only FHx Stroke was associated with previous hypertension (OR=1.59, 95%CI=1.08 to 2.35, P =0.02). FHx MI was more frequent in large-artery stroke (OR=1.63, 95%CI=0.99 to 2.69, P =0.05). Conclusion— Consistent results in our population-based studies and previous hospital-based studies suggest that inclusion bias is not a major problem for studies of the genetic epidemiology of stroke. Molecular genetic studies might be best targeted at non-cardioembolic stroke and younger patients. However, genetic susceptibility to hypertension may account for a significant proportion of the heritability of ischemic stroke.