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

Elizabeth Holliday, Jane Maguire, Tiffany Evans, Simon Koblar, Jim Jannes, Jonathan Sturm, Graeme Hankey, Ross Baker, Johnathan Golledge, Mark Parsons, Rainer Malik, Mark McEvoy, Erik Biros, Martin Lewis, Lisa Lincz, Roseanne Peel, Christopher Oldmeadow, Wayne Smith, Pablo Moscato, Simona BarleraSteven Bevan, Joshua Bis, Eric Boerwinkle, Giorgio Boncoraglio, Thomas Brott, Robert Brown, Yu Ching Chen, John Cole, Ioana Cotlarciuc, William Devan, Myriam Fornage, Karen Furie, Solveig Grétarsdóttir, Andreas Gschwendtner, Mohammad Ikram, William Longstreth, James Meschia, Braxton Mitchell, Thomas Mosley, Michael Nalls, Eugenio Parati, Bruce Psaty, Pankaj Sharma, K Stefansson, G Thorleifsson, Unnur Thorsteinsdottir, Matthew Traylor, Benjamin Verhaaren, Kerri Wiggins, Bradford Worrall, Cathie Sudlow, Peter Rothwell, Martin Farrall, Martin Dichgans, Jonathan Rosand, Hugh Markus, Rodney Scott, Christopher Levi, John Attia

    Research output: Contribution to journalArticle

    117 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1147-1151
    Number of pages5
    JournalNature Genetics
    Volume44
    Issue number10
    DOIs
    Publication statusPublished - Oct 2012

    Fingerprint Dive into the research topics of 'Common variants at 6p21.1 are associated with large artery atherosclerotic stroke'. Together they form a unique fingerprint.

    Cite this