Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes



Pulit, Sara L, Weng, Lu-Chen, McArdle, Patrick F, Trinquart, Ludovic, Choi, Seung Hoan, Mitchell, Braxton D, Rosand, Jonathan, de Bakker, Paul IW, Benjamin, Emelia J, Ellinor, Patrick T
et al (show 351 more authors) (2018) Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes. NEUROLOGY-GENETICS, 4 (6). e293-.

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Abstract

<h4>Objective</h4>We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk.<h4>Methods</h4>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.<h4>Results</h4>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 <i>p</i> < 4.4 × 10<sup>-4</sup> 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, <i>p</i> = 1.45 × 10<sup>-48</sup>), 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, <i>p</i> = 0.004), but no other primary stroke subtypes (all <i>p</i> > 0.1).<h4>Conclusions</h4>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: Article
Depositing User: Symplectic Admin
Date Deposited: 19 Feb 2020 13:22
Last Modified: 19 Jan 2023 00:02
DOI: 10.1212/NXG.0000000000000293
Open Access URL: https://doi.org/10.1212/NXG.0000000000000293
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3075727