Pulit, SL;
Weng, L-C;
McArdle, PF;
Trinquart, L;
Choi, SH;
Mitchell, BD;
Rosand, J;
... Sheth, K; + view all
(2018)
Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes.
Neurology Genetics
, 4
(6)
, Article e293. 10.1212/NXG.0000000000000293.
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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.
| Type: | Article |
|---|---|
| Title: | Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1212/NXG.0000000000000293 |
| Publisher version: | https://doi.org/10.1212/NXG.0000000000000293 |
| Language: | English |
| Additional information: | © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | All Clinical Neurology, All Cerebrovascular disease/Stroke, Case control studies, Embolism, Association studies in genetics |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10091531 |
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