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Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0001-5894-0351
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0003-2335-8542
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
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Number of Authors: 3612018 (English)In: NEUROLOGY-GENETICS, ISSN 2376-7839, Vol. 4, no 6, article id e293Article in journal (Refereed) Published
Abstract [en]

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 x 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 x 10(-48)), explaining similar to 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.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS , 2018. Vol. 4, no 6, article id e293
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Medical Genetics
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URN: urn:nbn:se:uu:diva-387247DOI: 10.1212/NXG.0000000000000293ISI: 000455099800017PubMedID: 30584597OAI: oai:DiVA.org:uu-387247DiVA, id: diva2:1331296
Note

For complete list of authors see http://dx.doi.org/10.1212/NXG.0000000000000293

Available from: 2019-06-26 Created: 2019-06-26 Last updated: 2019-06-26Bibliographically approved

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