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

UNLABELLED: 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). CONCLUSIONS: 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.