title: Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke.
abstract: OBJECTIVE
  To find sequence variants that associate with the risk for ischemic stroke (IS), we performed a genome-wide association study.
  
  
  METHODS
  We genotyped 1,661 Icelandic IS patients and 10,815 control subjects using the Infinium HumanHap300 chip (Illumina, San Diego, CA). A total of 310,881 single nucleotide polymorphisms (SNPs) were tested for association with IS, and the most significant signals were replicated in two large European IS sample sets (2,224 cases/2,583 control subjects). Two SNPs, rs2200733 and rs10033464, were tested further in additional European IS samples (2,327 patients and 16,760 control subjects).
  
  
  RESULTS
  In the Icelandic samples and the two replication sets combined, rs2200733 associated significantly with cardioembolic stroke (CES) (odds ratio [OR], 1.54; p = 8.05 x 10(-9)). No other variants associated with IS or any of its subtypes. rs2200733 associated significantly with IS in all sample sets combined (OR, 1.26; p = 2.18 x 10(-10)), and both rs2200733 and its neighbour, rs10033464 associated strongly with CES (rs2200733: OR, 1.52; p = 5.8 x 10(-12); rs10033464: OR, 1.27; p = 6.1 x 10(-4)). Interestingly, rs2200733 also showed significant association to IS not classified as CES.
  
  
  CONCLUSIONS
  We discovered that variants previously shown to associate with atrial fibrillation (AF), rs2200733 and rs10033464, significantly associated with IS, with the strongest risk for CES. The association with noncardiogenic stroke is intriguing and suggests that atrial fibrillation may be underdiagnosed in patients presenting with stroke. This discovery may have implications for workup and treatment of IS.
authors.affiliation: DeCODE Genetics, Reykjavik, Iceland. solveig.gretarsdottir@decode.is
authors.forename: Solveig
authors.initials: S
authors.lastname: Gretarsdottir
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: Andrei
authors.initials: A
authors.lastname: Manolescu
authors.forename: Unnur
authors.initials: U
authors.lastname: Styrkarsdottir
authors.forename: Anna
authors.initials: A
authors.lastname: Helgadottir
authors.forename: Andreas
authors.initials: A
authors.lastname: Gschwendtner
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kostulas
authors.forename: Gregor
authors.initials: G
authors.lastname: Kuhlenbäumer
authors.forename: Steve
authors.initials: S
authors.lastname: Bevan
authors.forename: Thorbjorg
authors.initials: T
authors.lastname: Jonsdottir
authors.forename: Hjordis
authors.initials: H
authors.lastname: Bjarnason
authors.forename: Jona
authors.initials: J
authors.lastname: Saemundsdottir
authors.forename: Stefan
authors.initials: S
authors.lastname: Palsson
authors.forename: David O
authors.initials: DO
authors.lastname: Arnar
authors.forename: Hilma
authors.initials: H
authors.lastname: Holm
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Thorgeirsson
authors.forename: Einar Mar
authors.initials: EM
authors.lastname: Valdimarsson
authors.forename: Sigurlaug
authors.initials: S
authors.lastname: Sveinbjörnsdottir
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Klaus
authors.initials: K
authors.lastname: Berger
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Jan
authors.initials: J
authors.lastname: Hillert
authors.forename: Hugh
authors.initials: H
authors.lastname: Markus
authors.forename: Jeffrey Robert
authors.initials: JR
authors.lastname: Gulcher
authors.forename: E Bernd
authors.initials: EB
authors.lastname: Ringelstein
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.forename: Daniel Fannar
authors.initials: DF
authors.lastname: Gudbjartsson
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D001281:Atrial Fibrillation / Q000150:complications / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4; D016001:Confidence Intervals; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000235:genetics*; D044465:White People / Q000235:genetics