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Polymorphisms and Noncardioembolic Stroke in Three Case-Control Studies

Luke M.M.a · Berger K.e · Rowland C.M.a · Catanese J.J.a · Tong C.H.a · Ross D.A.a · Garcia V.a · Kuhlenbaeumer G.f · Ringelstein E.B.f · Pullinger C.R.b · Malloy M.J.b · Deedwania P.c · Ellis S.G.d · Kane J.P.b · Devlin J.J.a · Lalouschek W.g · Mannhalter C.g
aCelera, Alameda, Calif., bCardiovascular Research Institute, UCSF, San Francisco, Calif., cDepartment of Medicine, UCSF Fresno, Fresno, Calif., and dThe Cleveland Clinic, Department of Cardiovascular Medicine, Cleveland, Ohio, USA; eInstitute of Epidemiology and Social Medicine and fDepartment of Neurology, University of Muenster, Germany; gMedical University Vienna, Vienna, Austria Cerebrovasc Dis 2012;33:80–85 (DOI:10.1159/000333444)


Background: Gene variants associated with disease could reveal novel mechanisms. We searched for single nucleotide polymorphisms (SNPs) associated with noncardioembolic stroke (nonCES). Methods: We tested 24,926 SNPs in or near genes for association with nonCES in the Vienna Study (551 cases, 815 controls) and then evaluated the associated SNPs in the UCSF-CC Study (570 cases, 1,604 controls) first in pooled DNA samples and then in individual DNA samples. We then asked whether the risk alleles of the SNPs associated with increased risk in both studies were also associated with increased risk of nonCES in the German Study (728 cases, 1,041 controls). Results: Six of the 46 SNPs that were associated with nonCES in both the Vienna and the UCSF-CC Studies were also associated with nonCES in the German Study: rs362277 in HTT (OR 1.39, 90% CI 1.12–1.71), rs2924914 near CSMD1 (OR 1.22, 90% CI 1.04–1.43), rs1264352 near DDR1 (OR 1.20, 90% CI 1.02–1.41), rs544115 in NEU3 (OR 1.63, 90% CI 1.02–2.62), rs12481805 in UMODL1 (OR 1.31, 90% CI 1.01–1.81), and rs2857595 near NCR3 (OR 1.15, 90% CI 1.00–1.32). Accounting for multiple testing of 46 SNPs, these 6 SNPs had a false discovery rate of 0.69. Conclusions: Some of the 6 SNPs may be associated with nonCES but most may be false positives. These 6 SNPs merit investigation in additional nonCES study populations.


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