PT  - JOURNAL ARTICLE
AU  - Pulit, Sara L.
AU  - Weng, Lu-Chen
AU  - McArdle, Patrick F.
AU  - Trinquart, Ludovic
AU  - Choi, Seung Hoan
AU  - Mitchell, Braxton D.
AU  - Rosand, Jonathan
AU  - de Bakker, Paul I. W.
AU  - Benjamin, Emelia J.
AU  - Ellinor, Patrick T.
AU  - Kittner, Steven J.
AU  - Lubitz, Steven A.
AU  - Anderson, Christopher D.
ED  - ,
TI  - Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
AID  - 10.1212/NXG.0000000000000293
DP  - 2018 Dec 01
TA  - Neurology Genetics
PG  - e293
VI  - 4
IP  - 6
4099  - http://ng.neurology.org/content/4/6/e293.short
4100  - http://ng.neurology.org/content/4/6/e293.full
SO  - Neurol Genet2018 Dec 01; 4
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