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Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke
Author(s) -
Gretarsdottir Solveig,
Thorleifsson Gudmar,
Manolescu Andrei,
Styrkarsdottir Unnur,
Helgadottir Anna,
Gschwendtner Andreas,
Kostulas Konstantinos,
Kuhlenbäumer Gregor,
Bevan Steve,
Jonsdottir Thorbjorg,
Bjarnason Hjordis,
Saemundsdottir Jona,
Palsson Stefan,
Arnar David O.,
Holm Hilma,
Thorgeirsson Gudmundur,
Valdimarsson Einar Mar,
Sveinbjörnsdottir Sigurlaug,
Gieger Christian,
Berger Klaus,
Wichmann HErich,
Hillert Jan,
Markus Hugh,
Gulcher Jeffrey Robert,
Ringelstein E. Bernd,
Kong Augustine,
Dichgans Martin,
Gudbjartsson Daniel Fannar,
Thorsteinsdottir Unnur,
Stefansson Kari
Publication year - 2008
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21480
Subject(s) - atrial fibrillation , single nucleotide polymorphism , stroke (engine) , ischemic stroke , medicine , odds ratio , case control study , cardiology , bioinformatics , genetics , genotype , biology , gene , ischemia , mechanical engineering , engineering
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 × 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 × 10 −10 ), and both rs2200733 and its neighbour, rs10033464 associated strongly with CES (rs2200733: OR, 1.52; p = 5.8 × 10 −12 ; rs10033464: OR, 1.27; p = 6.1 × 10 −4 ). Interestingly, rs2200733 also showed significant association to IS not classified as CES. Interpretation 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. Ann Neurol 2008;64:402–409