RT Journal Article
SR Electronic
T1 Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
JF Neurology Genetics
JO Neurol Genet
FD Lippincott Williams & Wilkins
SP e293
DO 10.1212/NXG.0000000000000293
VO 4
IS 6
A1 Pulit, Sara L.
A1 Weng, Lu-Chen
A1 McArdle, Patrick F.
A1 Trinquart, Ludovic
A1 Choi, Seung Hoan
A1 Mitchell, Braxton D.
A1 Rosand, Jonathan
A1 de Bakker, Paul I. W.
A1 Benjamin, Emelia J.
A1 Ellinor, Patrick T.
A1 Kittner, Steven J.
A1 Lubitz, Steven A.
A1 Anderson, Christopher D.
A1 ,
YR 2018
UL http://ng.neurology.org/content/4/6/e293.abstract
AB 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.AF=atrial fibrillation; AFGen=AF Genetics; CCS=Causative Classification System; CI=confidence interval; GRM=genetic relationship matrix; GWAS=genome-wide association studies; MAF=minor allele frequency; OR=odds ratio; PC=principal component; PRS=polygenic risk score; SiGN=Stroke Genetics Network