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

Abstract

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 (FHxStroke) and of myocardial infarction (FHxMI) in first-degree relatives in 2 population-based studies (Oxford Vascular Study [OXVASC]; Oxfordshire Community Stroke Project [OCSP]). We related FHxStroke and FHxMI to subtype of ischemic stroke, age, and the presence of vascular risk factors and performed a systematic review of all studies of FHxStroke by stroke subtype. Results - In our population-based studies and in 3 hospital-based studies, FHxStroke 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, FHxStroke (P=0.02), FHxMI (P=0.04), and FHx of either (P=0.006) were associated with stroke at a younger age. Only FHxStroke was associated with previous hypertension (OR=1.59, 95%CI=1.08 to 2.35, P=0.02). FHxMI 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.