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

Holliday, E.G., Maguire, J.M., Evans, T-J, Koblar, S.A., Jannes, J., Sturm, J.W., 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., Cheng, Y-C, Cole, J.W., Cotlarciuc, I., Devan, W.J., Fornage, M., Furie, K.L., Grétarsdóttir, S., Gschwendtner, A., Ikram, M.A., Longstreth, W.T., 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.J., 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. and Attia, J. (2012) Common variants at 6p21.1 are associated with large artery atherosclerotic stroke. Nature Genetics, 44 (10). pp. 1147-1151.

Link to Published Version: http://dx.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.

Publication Type: Journal Article
Murdoch Affiliation: Centre for Haemophilia and Thrombosis Research
Publisher: Nature Publishing Group
Copyright: © 2012 Nature America, Inc.
URI: http://researchrepository.murdoch.edu.au/id/eprint/11018
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