Common variants at 6p21.1 are associated with large artery atherosclerotic stroke

Journal Publication ResearchOnline@JCU
Holliday, Elizabeth G.;Maguire, Jane M.;Evans, Tiffany-Jane;Koblar, Simon A.;Jannes, Jim;Sturm, Jonathan W.;Hankey, Graeme J.;Baker, Ross;Golledge, Jonathan;Parsons, Mark W.;Malik, Rainer;McEvoy, Mark;Biros, Erik;Lewis, Martin D.;Lincz, Lisa F.;Peel, Roseanne;Oldmeadow, Christopher;Smith, Wayne;Moscato, Pablo;Barlera, Simona;Bevan, Steve;Bis, Joshua C.;Boerwinkle, Eric;Boncoraglio, Giorgio B.;Brott, Thomas G.;Brown, Robert D.;Cheng, Yu-Ching;Cole, John W.;Cotlarciuc, Ioanna;Devan, William J.;Fornage, Myriam;Furie, Karen L.;Grétarsdóttir, Sólveig;Gschwendtner, Andreas;Ikram, M. Arfan;Longstreth, W.T.;Meschia, James F.;Mitchell, Braxton D.;Mosley, Thomas H.;Nalls, Michael A.;Parati, Eugenio A.;Psaty, Bruce M.;Sharma, Pankaj;Stefansson, Kari;Thorleifsson, Gudmar;Thorsteinsdottir, Unnur;Traylor, Matthew;Verhaaren, Benjamin F.J.;Wiggins, Kerri L.;Worrall, Bradford B.;Sudlow, Cathie;Rothwell, Peter M.;Farrall, Martin;Dichgans, Martin;Rosand, Jonathan;Markus, Hugh S.;Scott, Rodney J.;Levi, Christopher;Attia, John
Jonathan Golledge
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 = 3.9 × 10(-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 = 3.9 × 10(-4); discovery and replication combined OR = 1.21, P = 4.7 × 10(-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.

Journal

Nature Genetics

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44

ISBN/ISSN

1546-1718

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Issue

10

Pages Count

5

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Publisher

Nature Publishing Group

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DOI

10.1038/ng.2397