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

E.G. Holliday; J.M. Maguire; T-J Evans; S.A. Koblar; J. Jannes; J.W. Sturm; G.J. Hankey; R. Baker; J. Golledge; M.W. Parsons; R. Malik; M. McEvoy; E. Biros; M.D. Lewis; L.F. Lincz; R. Peel; C. Oldmeadow; W. Smith; P. Moscato; S. Barlera; S. Bevan; J.C. Bis; E. Boerwinkle; G.B. Boncoraglio; T.G. Brott; R.D. Brown; Y-C Cheng; J.W. Cole; I. Cotlarciuc; W.J. Devan; M. Fornage; K.L. Furie; S. Grétarsdóttir; A. Gschwendtner; M.A. Ikram; W.T. Longstreth; J.F. Meschia; B.D. Mitchell; T.H. Mosley; M.A. Nalls; E.A. Parati; B.M. Psaty; P. Sharma; K. Stefansson; G. Thorleifsson; U. Thorsteinsdottir; M. Traylor; B.F.J. Verhaaren; K.L. Wiggins; B.B. Worrall; C. Sudlow; P.M. Rothwell; M. Farrall; M. Dichgans; J. Rosand; H.S. Markus; R.J. Scott; C. Levi; J. Attia

doi:10.1038/ng.2397

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

Journal article

Peer reviewed

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

E.G. Holliday, J.M. Maguire, T-J Evans, S.A. Koblar, J. Jannes, J.W. Sturm, G.J. Hankey, R. Baker, J. Golledge, M.W. Parsons, …

Nature Genetics, Vol.44(10), pp.1147-1151

2012

DOI: https://doi.org/10.1038/ng.2397

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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.

Details

Title: Common variants at 6p21.1 are associated with large artery atherosclerotic stroke
Authors/Creators: E.G. Holliday (Author/Creator) - University of Newcastle Australia
J.M. Maguire (Author/Creator) - University of Newcastle Australia
T-J Evans (Author/Creator) - University of Newcastle Australia
S.A. Koblar (Author/Creator) - The University of Adelaide
J. Jannes (Author/Creator) - The University of Adelaide
J.W. Sturm (Author/Creator) - University of Newcastle Australia
G.J. Hankey (Author/Creator) - The University of Western Australia
R. Baker (Author/Creator) - Murdoch University
J. Golledge (Author/Creator) - James Cook University
M.W. Parsons (Author/Creator)
R. Malik (Author/Creator) - Ludwig-Maximilians-Universität München
M. McEvoy (Author/Creator) - University of Newcastle Australia
E. Biros (Author/Creator) - James Cook University
M.D. Lewis (Author/Creator) - The University of Adelaide
L.F. Lincz (Author/Creator) - University of Newcastle Australia
R. Peel (Author/Creator) - University of Newcastle Australia
C. Oldmeadow (Author/Creator) - University of Newcastle Australia
W. Smith (Author/Creator) - University of Newcastle Australia
P. Moscato (Author/Creator) - University of Newcastle Australia
S. Barlera (Author/Creator) - Mario Negri Institute for Pharmacological Research
S. Bevan (Author/Creator) - St George's, University of London
J.C. Bis (Author/Creator) - University of Washington
E. Boerwinkle (Author/Creator) - The University of Texas Health Science Center at Houston
G.B. Boncoraglio (Author/Creator)
T.G. Brott (Author/Creator) - Mayo Clinic
R.D. Brown (Author/Creator) - Mayo Clinic
Y-C Cheng (Author/Creator) - University of Maryland, Baltimore
J.W. Cole (Author/Creator) - University of Maryland, Baltimore
I. Cotlarciuc (Author/Creator) - Imperial College London
W.J. Devan (Author/Creator) - Broad Institute
M. Fornage (Author/Creator) - The University of Texas Health Science Center at Houston
K.L. Furie (Author/Creator) - Harvard University
S. Grétarsdóttir (Author/Creator) - deCODE Genetics (Iceland)
A. Gschwendtner (Author/Creator) - Ludwig-Maximilians-Universität München
M.A. Ikram (Author/Creator) - Erasmus University Rotterdam
W.T. Longstreth (Author/Creator) - University of Washington
J.F. Meschia (Author/Creator) - Mayo Clinic
B.D. Mitchell (Author/Creator) - University of Maryland, Baltimore
T.H. Mosley (Author/Creator) - University of Mississippi
M.A. Nalls (Author/Creator) - National Institutes of Health
E.A. Parati (Author/Creator)
B.M. Psaty (Author/Creator) - University of Washington
P. Sharma (Author/Creator) - Imperial College London
K. Stefansson (Author/Creator) - University of Iceland
G. Thorleifsson (Author/Creator) - deCODE Genetics (Iceland)
U. Thorsteinsdottir (Author/Creator) - University of Iceland
M. Traylor (Author/Creator) - St George's, University of London
B.F.J. Verhaaren (Author/Creator) - Erasmus University Rotterdam
K.L. Wiggins (Author/Creator) - University of Washington
B.B. Worrall (Author/Creator) - University of Virginia
C. Sudlow (Author/Creator) - University of Edinburgh
P.M. Rothwell (Author/Creator) - University of Oxford
M. Farrall (Author/Creator) - University of Oxford
M. Dichgans (Author/Creator) - Ludwig-Maximilians-Universität München
J. Rosand (Author/Creator) - Broad Institute
H.S. Markus (Author/Creator) - St George's, University of London
R.J. Scott (Author/Creator) - University of Newcastle Australia
C. Levi (Author/Creator)
J. Attia (Author/Creator) - University of Newcastle Australia
Publication Details: Nature Genetics, Vol.44(10), pp.1147-1151
Publisher: Nature Publishing Group
Identifiers: 991005540818007891
Copyright: © 2012 Nature America, Inc.
Murdoch Affiliation: Centre for Haemophilia and Thrombosis Research
Language: English
Resource Type: Journal article

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.189 Genome Studies; 1.189.455 Genome-Wide Association Studies
Web Of Science research areas: Genetics & Heredity
ESI research areas: Molecular Biology & Genetics