1. Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke
- Author
-
Karen L. Furie, Thomas Meitinger, Paul D. Syme, Stephen S. Rich, Agnieszka Slowik, Mary Joan MacLeod, James F. Meschia, Mar Matarin, Martin Dichgans, S. J. Kittner, Hugh S. Markus, Braxton D. Mitchell, Anna Plourde, Bertram Müller-Myhsok, Jonathan Rosand, Erich Wichmann, Steve Bevan, Helen Ross-Adams, Andreas Gschwendtner, and John W. Cole
- Subjects
Male ,medicine.medical_specialty ,Pathology ,Genotype ,Genome-wide association study ,Locus (genetics) ,Coronary Artery Disease ,Biology ,Polymorphism, Single Nucleotide ,Risk Assessment ,Article ,Coronary artery disease ,Gene Frequency ,Risk Factors ,Internal medicine ,Ethnicity ,Odds Ratio ,medicine ,Humans ,Genetic Predisposition to Disease ,cardiovascular diseases ,Myocardial infarction ,Stroke ,Vascular disease ,Chromosome Mapping ,Odds ratio ,medicine.disease ,Europe ,Neurology ,North America ,Cardiology ,Female ,Neurology (clinical) ,Chromosomes, Human, Pair 9 ,Risk assessment - Abstract
Recent studies have identified a major locus for risk for coronary artery disease and myocardial infarction 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.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.Genotyping of the screening samples demonstrated associations between seven SNPs and atherosclerotic stroke (all p0.05). 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 p0.05). 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.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.
- Published
- 2009
- Full Text
- View/download PDF