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Title: Common variants at 6p21.1 are associated with large artery atherosclerotic stroke
Authors: Sturm, Jonathan ;Maguire, Jane M ;Holliday, E.G.;Evans, T.J.;Koblar, Simon A ;Jannes, J.;Hankey, G.J.;Baker, R.;Golledge, J.;Parsons, M.W.;Malik, R.;McEvoy, M.;Biros, E.;Lewis, M.D.;Lincz, L.F.;Peel, R.;Oldmeadow, C.;Smith, W.;Moscato, P.;Barlera, S.;Bevan, S.;Bis, J.C.;Boerwinkle, E.;Boncoraglio, G.B.;Brott, T.G.;Brown, R.D., Jr;Cheng, Y.C.;Cole, J.W.;Cotlarciuc, I.;Devan, W.J.;Fornage, M.;Furie, K.L.;Gretarsdottir, S.;Gschwendtner, A.;Ikram, M.A.;Longstreth, W.T., Jr.;Meschia, J.F.;Mitchell, B.D.;Mosley, T.H.;Nalls, M.A.;Parati, E.A.;Psaty, B.M.;Sharma, P.;Stefansson, K.;Thorleifsson, G.;Thorsteinsdottir, U.;Traylor, M.;Verhaaren, B.F.;Wiggins, K.L.;Worrall, B.B.;Sudlow, C.;Rothwell, P.M.;Farrall, M.;Dichgans, M.;Rosand, J.;Markus, H.S.;Scott, R.J.;Levi, C.;Attia, J.
Issue Date: Oct-2012
Source: Volume 44, Issue 10, pp. 1147 - 1151
Journal title: Nature Genetics
Abstract: Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke cases (including 421 LAA cases) and 1,244 population controls from Australia. Evidence for a genetic influence on ischemic stroke risk was detected, but this influence was higher and more significant for the LAA subtype. We identified a new LAA susceptibility locus on chromosome 6p21.1 (rs556621: odds ratio (OR)=1.62, P=3.9x10(-8)) and replicated this association in 1,715 LAA cases and 52,695 population controls from 10 independent population cohorts (meta-analysis replication OR=1.15, P=3.9x10(-4); discovery and replication combined OR=1.21, P=4.7x10(-8)). This study identifies a genetic risk locus for LAA and shows how analyzing etiological subtypes may better identify genetic risk alleles for ischemic stroke.
DOI: 10.1038/ng.2397
ISSN: 1546-1718
Publicaton type: Journal Article
Keywords: Stroke
Genetic Diseases
Study or Trial: Meta-Analysis
Appears in Collections:Neurology

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