TY - JOUR
T1 - Evaluating the genetic component of ischemic stroke subtypes
T2 - A family history study
AU - Jerrard-Dunne, Paula
AU - Cloud, Geoffrey
AU - Hassan, Ahamad
AU - Markus, Hugh S.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - Background and Purpose - Twin and family history studies support a role for genetic factors in stroke risk. Because the etiology of ischemic stroke is heterogeneous, genetic factors may vary by etiologic subtype. We determined the familial aggregation of stroke risk in different stroke phenotypes and used the results to model estimated sample size requirements for case-control studies. Methods - One thousand consecutive white subjects with ischemic stroke and 800 white controls matched for age and sex were recruited. A first-degree family history of stroke and myocardial infarction was obtained by structured interview. Stroke subtype was determined with the use of modified Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Results - A family history of stroke at ≤65 years was a significant risk factor for large-vessel disease (odds ratio [OR], 2.24; 95% CI, 1.49 to 3.36; P<0.001) and for small-vessel disease (OR, 1.93; 95% CI, 1.25 to 2.97; P=0.003). When only cases aged ≤65 years were considered, these ORs increased to 2.93 (95% CI, 1.68 to 5.13) (P<0.001) and 3.15 (95% CI, 1.81 to 5.50) (P<0.001), respectively. No significant associations were seen for cardioembolic stroke or stroke of undetermined etiology. Conclusions - A family history of vascular disease is an independent risk factor for both large-vessel atherosclerosis and small-vessel disease, especially in cases presenting before age 65 years. The estimated sample sizes for case-control studies illustrate how candidate gene studies for ischemic stroke might be made more effective by focusing on these specific phenotypes, in which the genetic component of the disease appears to be strongest.
AB - Background and Purpose - Twin and family history studies support a role for genetic factors in stroke risk. Because the etiology of ischemic stroke is heterogeneous, genetic factors may vary by etiologic subtype. We determined the familial aggregation of stroke risk in different stroke phenotypes and used the results to model estimated sample size requirements for case-control studies. Methods - One thousand consecutive white subjects with ischemic stroke and 800 white controls matched for age and sex were recruited. A first-degree family history of stroke and myocardial infarction was obtained by structured interview. Stroke subtype was determined with the use of modified Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Results - A family history of stroke at ≤65 years was a significant risk factor for large-vessel disease (odds ratio [OR], 2.24; 95% CI, 1.49 to 3.36; P<0.001) and for small-vessel disease (OR, 1.93; 95% CI, 1.25 to 2.97; P=0.003). When only cases aged ≤65 years were considered, these ORs increased to 2.93 (95% CI, 1.68 to 5.13) (P<0.001) and 3.15 (95% CI, 1.81 to 5.50) (P<0.001), respectively. No significant associations were seen for cardioembolic stroke or stroke of undetermined etiology. Conclusions - A family history of vascular disease is an independent risk factor for both large-vessel atherosclerosis and small-vessel disease, especially in cases presenting before age 65 years. The estimated sample sizes for case-control studies illustrate how candidate gene studies for ischemic stroke might be made more effective by focusing on these specific phenotypes, in which the genetic component of the disease appears to be strongest.
KW - Cerebral infarction
KW - Epidemiology
KW - Genetics
KW - Risk factors
KW - Stroke classification
UR - http://www.scopus.com/inward/record.url?scp=0037534908&partnerID=8YFLogxK
U2 - 10.1161/01.STR.0000069723.17984.FD
DO - 10.1161/01.STR.0000069723.17984.FD
M3 - Article
C2 - 12714707
AN - SCOPUS:0037534908
VL - 34
SP - 1364
EP - 1369
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 6
ER -