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- Title
Common variants at 6p21.1 are associated with large artery atherosclerotic stroke.
- Authors
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
- 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.
- Subjects
HUMAN genetic variation; ATHEROSCLEROSIS; STROKE risk factors; ETIOLOGY of diseases; DISEASE susceptibility; CHROMOSOMES
- Publication
Nature Genetics, 2012, Vol 44, Issue 10, p1147
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.2397