TY - JOUR
T1 - Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
AU - Atrial Fibrillation Genetics Conso
AU - Int Stroke Genetics Consortium
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.
AU - Christophersen, Ingrid E.
AU - Rienstra, Michiel
AU - Roselli, Carolina
AU - Yin, Xiaoyan
AU - Geelhoed, Bastiaan
AU - Barnard, John
AU - Lin, Honghuang
AU - Arking, Dan E.
AU - Smith, Albert
AU - Albert, Christine M.
AU - Chaffin, Mark
AU - Tucker, Nathan R.
AU - Li, Molong
AU - Klarin, Derek
AU - Bihlmeyer, Nathan A.
AU - Low, Siew-Kee
AU - Weeke, Peter E.
AU - Mueller-Nurasyid, Martina
AU - Smith, J. Gustav
AU - Brody, Jennifer A.
AU - Niemeijer, Maartje N.
AU - Doerr, Marcus
AU - Trompet, Stella
AU - Huffman, Jennifer
AU - Gustafsson, Stefan
AU - Schurmann, Claudia
AU - Kleber, Marcus E.
AU - Lyytikainen, Leo-Pekka
AU - Seppala, Ilkka
AU - Malik, Rainer
AU - Hagemeijer, Yanick P.
AU - Verweij, Niek
AU - Siland, Joylene E.
AU - Huang, Jie
AU - Chen, Lin Y.
AU - van der Harst, Pim
AU - Brouwers, Bart
PY - 2018/12
Y1 - 2018/12
N2 - ObjectiveWe sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk.MethodsWe 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.ResultsWe 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 x 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 x 10(-48)), explaining similar to 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).ConclusionsGenetic 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.
AB - ObjectiveWe sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk.MethodsWe 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.ResultsWe 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 x 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 x 10(-48)), explaining similar to 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).ConclusionsGenetic 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.
KW - ISCHEMIC-STROKE
KW - CAUSATIVE CLASSIFICATION
KW - LIFETIME RISK
KW - EPIDEMIOLOGY
KW - ASSOCIATION
KW - PREVENTION
KW - VARIANTS
KW - ASPIRIN
KW - BURDEN
U2 - 10.1212/NXG.0000000000000293
DO - 10.1212/NXG.0000000000000293
M3 - Article
SN - 2376-7839
VL - 4
JO - Neurology. Genetics
JF - Neurology. Genetics
IS - 6
M1 - 293
ER -