on March 13, 2008
Published online before print March 13, 2008, doi: 10.1161/STROKEAHA.107.502963
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Submitted on August 30, 2007
From the Molecular Genetics Unit (M.M., A.S.), Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Porter Neuroscience Research Center, Bethesda, Md; the Section on Biostatistics (W.M.B.), Department of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, NC; the Reta Lila Weston Institute of Neurological Studies (J.A.H.), Institute of Neurology, University College London, London, UK; and the Department of Neurology (J.F.M.), Mayo Clinic, Jacksonville, Fla. * To whom correspondence should be addressed. E-mail: delmarm{at}mail.nih.gov.
Background and Purpose—Recently independent studies reported an association between coronary heart disease and single-nucleotide polymorphisms (SNPs) located at chromosome 9p21, near CDKN2A and CDKN2B genes. Given that stroke is a common complication after myocardial infarction, we investigated if the same SNPs were associated with ischemic stroke in our population. Methods—We recently initiated a whole genome analysis of ischemic stroke and published the first stage of a case control study using >400 000 SNPs from Illumina Infinium Human-1 and HumanHap300 assays. We focused on SNPs recently associated with heart disease by Helgadottir and colleagues and SNPs from the same haplotype block. Results—In analyses both unadjusted and adjusted for stroke risk factors, significant associations with ischemic stroke were observed for SNPs from the same haplotype block previously associated with myocardial infarction. Significant association was also seen between disease and haplotypes involving these SNPs, both with and without adjustment for stroke risk factors (odd ratios: 1.01 to 2.65). Conclusions—These data are important for 3 reasons: first, they suggest a genetic association for stroke; second, they suggest that this association shares pathogenic mechanisms with heart disease and diabetes; and third, they illustrate, that public release of data can facilitate rapid risk locus discovery.
Revised on October 31, 2007
Accepted on November 1, 2007
Whole Genome Analyses Suggest Ischemic Stroke and Heart Disease Share an Association With Polymorphisms on Chromosome 9p21
Mar Matarin PhD*;
Key words: ischemic stroke • genetics • heart disease • diabetes