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Objective:We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. Methods:We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. Results:We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 × 10-4 in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 × 10-48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07, p = 0.004), but no other primary stroke subtypes (all p > 0.1). Conclusions:Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.

Original publication

DOI

10.1212/NXG.0000000000000293

Type

Journal article

Journal

Neurology. Genetics

Publication Date

03/12/2018

Volume

4

Pages

e293 - e293

Addresses

Department of Genetics (S.L.P., P.I.W.d. B.), University Medical Center Utrecht, Utrecht University, The Netherlands; P.I.W.d.B. is now with Computational Genomics, Vertex Pharmaceuticals, Boston, MA; Li Ka Shing Centre for Health Information and Discovery (S.L.P.), The Big Data Institute, University of Oxford, United Kingdom; Program in Medical and Population Genetics (S.L.P., L.-C.W., S.H.C., J.R., P.T.E., S.A.L., C.D.A.), Broad Institute, Cambridge, MA; Cardiovascular Research Center (L.-C.W., P.T.E., S.A.L.), Center for Genomic Medicine (J.R., C.D.A.), J.P. Kistler Stroke Research Center (J.R., C.D.A.), and Cardiac Arrhythmia Service (P.T.E., S.A.L.), Massachusetts General Hospital, Boston; Department of Medicine (P.F.M., B.D.M.), Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study (L.T., E.J.B.); Department of Biostatistics (L.T.) and Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Geriatrics Research and Education Clinical Center (B.D.M.), Baltimore Veterans Administration Medical Center, MD; Cardiology Preventive Medicine Sections (E.J.B.), Evans Department of Medicine, Boston University School of Medicine; Department of Neurology (S.J.K.), University of Maryland School of Medicine; and Department of Neurology (S.J.K.), Veterans Affairs Medical Center, Baltimore, MD.