Atrial Fibrillation Genetic Risk and Ischemic Stroke Mechanisms

Steven A. Lubitz, Owen Parsons, Christopher D. Anderson, Emelia J. Benjamin, Rainer Malik, Lu-Chen Weng, Martin Dichgans, Catherine Sudlow, Peter M. W. Rothwell, Jonathan Rosand, Patrick T Ellinor, Hugh S. Markus, Matthew Traylor

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Purpose: Atrial fibrillation (AF) is a leading cause of cardioembolic stroke, but the relations between AF and non-cardioembolic stroke subtypes are unclear. Since AF may be unrecognized, and because AF has a substantial genetic basis, we assessed for predisposition to AF across ischemic stroke subtypes. Methods: We examined associations between AF genetic risk and Trial of Org 10172 in Acute Stroke Treatment stroke subtypes in 2,374 ambulatory individuals with ischemic stroke and 5,175 without from the Wellcome Trust Case-Control Consortium 2 using logistic regression. We calculated AF genetic risk scores using single nucleotide polymorphisms (SNPs) associated with AF in a prior independent analysis across a range of preselected significance thresholds. Results: There were 460 (19.4%) individuals with cardioembolic, 498 (21.0%) with large vessel, 474 (20.0%) with small vessel, and 814 (32.3%) with strokes of undetermined cause. Most AF genetic risk scores were associated with stroke, with the strongest association (P=6x10-4) attributed to scores of 944 SNPs (each associated with AF at P<1x10-3 in a prior analysis). Associations between AF genetic risk and stroke were enriched in the cardioembolic stroke subset (strongest P=1.2x10-9, 944 SNP score). In contrast, AF genetic risk was not significantly associated with non-cardioembolic stroke subtypes. Conclusions: Comprehensive AF genetic risk scores were specific for cardioembolic stroke. Incomplete workups and subtype misclassification may have limited the power to detect associations with strokes of undetermined etiology. Future studies are warranted to determine whether AF genetic risk is a useful biomarker to enhance clinical discrimination of stroke etiologies
Original languageEnglish
JournalStroke
Early online date3 May 2017
DOIs
Publication statusE-pub ahead of print - 3 May 2017

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