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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Abstract
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). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Macfarlane, Professor Peter and Padmanabhan, Professor Sandosh and Ford, Professor Ian and Walters, Professor Matthew |
| 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 > School of Health & Wellbeing > Robertson Centre College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing |
| Journal Name: | Neurology Genetics |
| Publisher: | Lippincott, Williams & Wilkins |
| ISSN: | 2376-7839 |
| 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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