Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke.

2.50
Hdl Handle:
http://hdl.handle.net/2336/42215
Title:
Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke.
Authors:
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, H-Erich; Hillert, Jan; Markus, Hugh; Gulcher, Jeffrey Robert; Ringelstein, E Bernd; Kong, Augustine; Dichgans, Martin; Gudbjartsson, Daniel Fannar; Thorsteinsdottir, Unnur; Stefansson, Kari
Citation:
Ann. Neurol. 2008, 64(4):402-9
Issue Date:
1-Oct-2008
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. 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.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://dx.doi.org/10.1002/ana.21480

Full metadata record

DC FieldValue Language
dc.contributor.authorGretarsdottir, Solveig-
dc.contributor.authorThorleifsson, Gudmar-
dc.contributor.authorManolescu, Andrei-
dc.contributor.authorStyrkarsdottir, Unnur-
dc.contributor.authorHelgadottir, Anna-
dc.contributor.authorGschwendtner, Andreas-
dc.contributor.authorKostulas, Konstantinos-
dc.contributor.authorKuhlenbäumer, Gregor-
dc.contributor.authorBevan, Steve-
dc.contributor.authorJonsdottir, Thorbjorg-
dc.contributor.authorBjarnason, Hjordis-
dc.contributor.authorSaemundsdottir, Jona-
dc.contributor.authorPalsson, Stefan-
dc.contributor.authorArnar, David O-
dc.contributor.authorHolm, Hilma-
dc.contributor.authorThorgeirsson, Gudmundur-
dc.contributor.authorValdimarsson, Einar Mar-
dc.contributor.authorSveinbjörnsdottir, Sigurlaug-
dc.contributor.authorGieger, Christian-
dc.contributor.authorBerger, Klaus-
dc.contributor.authorWichmann, H-Erich-
dc.contributor.authorHillert, Jan-
dc.contributor.authorMarkus, Hugh-
dc.contributor.authorGulcher, Jeffrey Robert-
dc.contributor.authorRingelstein, E Bernd-
dc.contributor.authorKong, Augustine-
dc.contributor.authorDichgans, Martin-
dc.contributor.authorGudbjartsson, Daniel Fannar-
dc.contributor.authorThorsteinsdottir, Unnur-
dc.contributor.authorStefansson, Kari-
dc.date.accessioned2008-12-11T09:38:12Z-
dc.date.available2008-12-11T09:38:12Z-
dc.date.issued2008-10-01-
dc.date.submitted2008-12-11-
dc.identifier.citationAnn. Neurol. 2008, 64(4):402-9en
dc.identifier.issn0364-5134-
dc.identifier.pmid18991354-
dc.identifier.doi10.1002/ana.21480-
dc.identifier.urihttp://hdl.handle.net/2336/42215-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractOBJECTIVE: 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. 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.en
dc.language.isoenen
dc.publisherWiley-Lissen
dc.relation.urlhttp://dx.doi.org/10.1002/ana.21480en
dc.subject.meshPubMed - in processen
dc.titleRisk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke.en
dc.typeArticleen
dc.identifier.eissn1531-8249-
dc.contributor.departmentDeCODE Genetics, Reykjavik, Iceland. solveig.gretarsdottir@decode.isen
dc.identifier.journalAnnals of neurologyen

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