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).


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.
Stroke Prevention Research Unit, Department of Clinical Neurology, Radcliffe Infirmary, Woodstock Road, Oxford, UK.
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Schulz
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Flossmann
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Rothwell
D000367:Age Factors; D017668:Age of Onset; D002545:Brain Ischemia / Q000453:epidemiology* / Q000235:genetics; D002318:Cardiovascular Diseases / Q000150:complications* / Q000235:genetics; D006801:Humans; D015994:Incidence; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics; D015995:Prevalence; D012307:Risk Factors; D020521:Stroke / Q000145:classification / Q000453:epidemiology* / Q000235:genetics