title: Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-Universität, Marchioninistrasse 15, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Gschwendtner
authors.forename: Steve
authors.initials: S
authors.lastname: Bevan
authors.forename: John W
authors.initials: JW
authors.lastname: Cole
authors.forename: Anna
authors.initials: A
authors.lastname: Plourde
authors.forename: Mar
authors.initials: M
authors.lastname: Matarin
authors.forename: Helen
authors.initials: H
authors.lastname: Ross-Adams
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Erich
authors.initials: E
authors.lastname: Wichmann
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Karen
authors.initials: K
authors.lastname: Furie
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Slowik
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Paul D
authors.initials: PD
authors.lastname: Syme
authors.forename: Mary J
authors.initials: MJ
authors.lastname: MacLeod
authors.forename: James F
authors.initials: JF
authors.lastname: Meschia
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Kittner
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Markus
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
mesh_terms: D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003324:Coronary Artery Disease / Q000150:complications* / Q000235:genetics; D005006:Ethnicity; D005060:Europe / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009656:North America / Q000453:epidemiology; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000209:etiology* / Q000235:genetics*