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bioRxiv · 10.1101/239269

Shared Genetic Contributions to Atrial Fibrillation and Ischemic Stroke Risk

Pulit, S. L.·Weng, L.-C.·McArdle, P. F.·Trinquart, L.·Huan Choi, S.·Mitchell, B. D.·Rosand, J.·de Bakker, P. I.·Benjamin, E. J.·Ellinor, P. T.·Kittner, S. J.·Lubitz, S. A.·Anderson, C. D.·Atrial Fibrillation Genetics Consortium,·International Stroke Genetics Consortium,
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Abstract

ObjectiveWe sought to assess whether genetic risk factors for atrial fibrillation can explain cardioembolic stroke risk.\n\nMethodsWe evaluated genetic correlations between a prior 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.\n\nResultsWe observed strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearsons r=0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10-4 in the prior AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio (OR) per standard deviation (sd) = 1.40, p = 1.45x10-48), 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).\n\nConclusionsGenetic risk for 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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Pulit, S. L., Weng, L.-C., McArdle, P. F., Trinquart, L., Huan Choi, S., Mitchell, B. D., Rosand, J., de Bakker, P. I., Benjamin, E. J., Ellinor, P. T., Kittner, S. J., Lubitz, S. A., Anderson, C. D., Atrial Fibrillation Genetics Consortium,, International Stroke Genetics Consortium,. 2017-12-24. Shared Genetic Contributions to Atrial Fibrillation and Ischemic Stroke Risk. https://doi.org/10.1101/239269

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