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Pulit, S.L.* ; Weng, L.C.* ; McArdle, P.F.* ; Trinquart, L.* ; Choi, S.H.* ; Mitchell, B.D.* ; Rosand, J.* ; de Bakker, P.I.W.* ; Benjamin, E.J.* ; Ellinor, P.T.* ; Kittner, S.J.* ; Lubitz, S.A.* ; Anderson, C.D.* ; AFGen Consortium (Roselli, C. ; Müller-Nurasyid, M. ; Perz, S. ; Waldenberger, M. ; Lichtner, P. ; Peters, A. ; Kriebel, J.)

Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes.

Neurol. Genet. 4:e293 (2018)

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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.

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