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_name
Nat Genetjournal_title
Nature geneticsauthors
Holliday EG,Maguire JM,Evans TJ,Koblar SA,Jannes J,Sturm JW,Hankey GJ,Baker R,Golledge J,Parsons MW,Malik R,McEvoy M,Biros E,Lewis MD,Lincz LF,Peel R,Oldmeadow C,Smith W,Moscato P,Barlera S,Bevan S,Bis JC,Boerdoi
10.1038/ng.2397subject
Has Abstractpub_date
2012-10-01 00:00:00pages
1147-51issue
10eissn
1061-4036issn
1546-1718pii
ng.2397journal_volume
44pub_type
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