Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

Pulit, S. L. et al. (2018) Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes. Neurology Genetics, 4(6), e293. (doi: 10.1212/NXG.0000000000000293) (PMID:30584597) (PMCID:PMC6283455)

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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.

Item Type:Articles
Additional Information:Padmanabhan, S., Ford, I. and Macfarlane, P.W. are members of the Atrial Fibrillation Genetics (AFGen) Consortium. Walters, M. is a member of the International Stroke Genetics Consortium (ISGC).
Glasgow Author(s) Enlighten ID:Macfarlane, Professor Peter and Walters, Professor Matthew and Ford, Professor Ian and Padmanabhan, Professor Sandosh
Authors: Pulit, S. L., Weng, L.-C., McArdle, P. F., Trinquart, L., Choi, S. H., Mitchell, B. D., Rosand, J., de Bakker, P. I. W., Benjamin, E. J., Ellinor, P. T., Kittner, S. J., Lubitz, S. A., Anderson, C. D., Padmanabhan, S., Ford, I., Macfarlane, P. W., and Walters, M.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Neurology Genetics
Publisher:Lippincott, Williams & Wilkins
ISSN (Online):2376-7839
Published Online:03 December 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Nature Genetics 4(6): e293
Publisher Policy:Reproduced under a Creative Commons License

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