Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
AuthorPulit, SL; Weng, L-C; McArdle, PF; Trinquart, L; Choi, SH; Mitchell, BD; Rosand, J; de Bakker, PIW; Benjamin, EJ; Ellinor, PT; ...
Source TitleNeurology Genetics
PublisherLIPPINCOTT WILLIAMS & WILKINS
University of Melbourne Author/sThijs, Vincent
AffiliationFlorey Department of Neuroscience and Mental Health
Document TypeJournal Article
CitationsPulit, 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., Christophersen, I. E., Rienstra, M., Roselli, C., Yin, X., Geelhoed, B., Barnard, J. ,... Sheth, K. (2018). Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes. NEUROLOGY-GENETICS, 4 (6), https://doi.org/10.1212/NXG.0000000000000293.
Access StatusOpen Access
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.
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