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Gschwendtner, A.* ; Bevan, S.* ; Cole, J.W.* ; Plourde, A.* ; Matarin, M.* ; Ross-Adams, H.* ; Meitinger, T. ; Wichmann, H.-E. ; Mitchell, B.D.* ; Furie, K.* ; Slowik, A.* ; Rich, S.S.* ; Syme, P.D.* ; MacLeod, M.J.* ; Meschia, J.F.* ; Rosand, J.* ; Kittner, S.J.* ; Markus, H.S.* ; Müller-Myhsok, B.* ; Dichgans, M.*

Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke.

Ann. Neurol. 65, 531-539 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Recent studies have identified a major locus for risk for coronary artery disease and myocardial infiarction on chromosome 9p21.3. Stroke, in particular, ischemic stroke caused by atherosclerotic disease, shares common mechanisms with myocardial infarction. We investigated whether the 9p21 region contributes to ischemic stroke risk. Methods: In an initial screen, 15 single nucleotide polymorphisms (SNPs) covering the critical genetic interval on 9p21 were genotyped in samples from Southern Germany (1,090 cases, 1,244 control subjects) and the United Kingdom (758 cases, 872 control subjects, 3 SNPs). SNPs significantly associated with ischemic stroke or individual stroke subtypes in either of the screening samples were Subsequently genotyped in 2,528 additional cases and 2,189 additional control Subjects from Europe and North America. Results: Genotyping of the screening samples demonstrated associations between seven SNPs and atherosclerotic stroke (all p < 0.05). Analysis of the full sample confirmed associations between six SNPs and atherosclerotic stroke in multivariate analyses controlling for demographic variables, coronary, artery disease, myocardial infarction, and vascular risk factors (all p < 0.05). The odds ratios for the lead SNP (rs1537378-C) were similar in the various subsamples with a pooled odds ratio of 1.21 (95% confidence interval, 1.07-1.37) under both fixed- and random-effects models (p = 0.002). The point estimate for the population attributable risk is 20.1% For atherosclerotic stroke. Interpretation: The chromosome 9p21.3 region represents a major risk locus for atherosclerotic stroke. The effect of this locus on stroke appears to be independent of its relation to coronary artery disease and other stroke risk factors. Our findings support a broad role of the 9p21 region in arterial disease.
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Publication type Article: Journal article
Document type Scientific Article
Keywords genome-wide association; coronary-artery-disease; transient ischemic attack; smooth-muscle-cells; myocardial-infarction; cardiovascular events; plaque vulnerability; media thickness; metaanalysis; replication
Language english
Publication Year 2009
HGF-reported in Year 2009
ISSN (print) / ISBN 0364-5134
e-ISSN 1531-8249
Journal Annals of Neurology
Quellenangaben Volume: 65, Issue: 5, Pages: 531-539 Article Number: , Supplement: ,
Publisher Wiley
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30503 - Chronic Diseases of the Lung and Allergies
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500700-001
G-503900-001
DOI 10.1002/ana.21590
Scopus ID 67249112107
PubMed ID 19475673
Erfassungsdatum 2009-07-09
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