Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

Sara L. Pulit, Lu-Chen Weng, Patrick F. McArdle, Ludovic Trinquart, Seung Hoan Choi, Braxton D. Mitchell, Jonathan Rosand, Paul I. W. de Bakker, Emelia J. Benjamin, Patrick T. Ellinor, Steven J. Kittner, Steven A. Lubitz*, Christopher D. Anderson*, Ingrid E. Christophersen, Michiel Rienstra, Carolina Roselli, Xiaoyan Yin, Bastiaan Geelhoed, John Barnard, Honghuang LinDan E. Arking, Albert Smith, Christine M. Albert, Mark Chaffin, Nathan R. Tucker, Molong Li, Derek Klarin, Nathan A. Bihlmeyer, Siew-Kee Low, Peter E. Weeke, Martina Muller-Nurasyid, J. Gustav Smith, Jennifer A. Brody, Maartje N. Niemeijer, Marcus Dorr, Stella Trompet, Jennifer Huffman, Stefan Gustafsson, Claudia Schurmann, Marcus E. Kleber, Leo-Pekka Lyytikainen, Ilkka Seppala, Rainer Malik, Andrea R. V. R. Horimoto, Marco Perez, Juha Sinisalo, Stefanie Aeschbacher, Sebastien Theriault, Lin Y. Chen, Julie Staals, Atrial Fibrillation Genetics Conso; Int Stroke Genetics Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Article number293
Number of pages8
JournalNeurology. Genetics
Issue number6
Publication statusPublished - 1 Dec 2018




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