房颤遗传风险可区分心源性栓塞性卒中与其他卒中亚型。
Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes.
作者信息
Pulit Sara L, Weng Lu-Chen, McArdle Patrick F, Trinquart Ludovic, Choi Seung Hoan, Mitchell Braxton D, Rosand Jonathan, de Bakker Paul I W, Benjamin Emelia J, Ellinor Patrick T, Kittner Steven J, Lubitz Steven A, Anderson Christopher D
机构信息
Department of Genetics (S.L.P., P.I.W.d. B.), University Medical Center Utrecht, Utrecht University, The Netherlands; P.I.W.d.B. is now with Computational Genomics, Vertex Pharmaceuticals, Boston, MA; Li Ka Shing Centre for Health Information and Discovery (S.L.P.), The Big Data Institute, University of Oxford, United Kingdom; Program in Medical and Population Genetics (S.L.P., L.-C.W., S.H.C., J.R., P.T.E., S.A.L., C.D.A.), Broad Institute, Cambridge, MA; Cardiovascular Research Center (L.-C.W., P.T.E., S.A.L.), Center for Genomic Medicine (J.R., C.D.A.), J.P. Kistler Stroke Research Center (J.R., C.D.A.), and Cardiac Arrhythmia Service (P.T.E., S.A.L.), Massachusetts General Hospital, Boston; Department of Medicine (P.F.M., B.D.M.), Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study (L.T., E.J.B.); Department of Biostatistics (L.T.) and Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Geriatrics Research and Education Clinical Center (B.D.M.), Baltimore Veterans Administration Medical Center, MD; Cardiology Preventive Medicine Sections (E.J.B.), Evans Department of Medicine, Boston University School of Medicine; Department of Neurology (S.J.K.), University of Maryland School of Medicine; and Department of Neurology (S.J.K.), Veterans Affairs Medical Center, Baltimore, MD.
出版信息
Neurol Genet. 2018 Dec 3;4(6):e293. doi: 10.1212/NXG.0000000000000293. eCollection 2018 Dec.
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 < 4.4 × 10 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, = 1.45 × 10), 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, = 0.004), but no other primary stroke subtypes (all > 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.
目的
我们试图评估心房颤动（AF）的遗传风险因素是否能解释心源性栓塞性卒中的风险。
方法
我们使用来自卒中遗传学网络的全基因组基因型（3190例AF病例、3000例心源性栓塞性卒中病例和28026例对照），评估先前AF基因研究与存在心源性栓塞性卒中时的AF之间的遗传相关性。在考虑AF临床风险因素后，我们测试了先前验证的AF多基因风险评分（PRS）是否与心源性栓塞性卒中和其他卒中亚型相关。
结果
我们观察到先前报道的AF遗传风险、存在卒中时的AF与心源性栓塞性卒中之间存在强相关性（在先前AF荟萃分析中，SNP的Pearson相关系数r分别为0.77和0.76，P<4.4×10）。校正AF临床风险因素后的AF PRS与心源性栓塞性卒中相关（每标准差的比值比[OR]=1.40，P=1.45×10），解释了心源性栓塞性卒中风险遗传成分的约20%。AF PRS也与病因不明的卒中相关（每标准差的OR=1.07，P=0.004），但与其他原发性卒中亚型无关（所有P>0.1）。
结论
AF的遗传风险与心源性栓塞性卒中相关，独立于临床风险因素。有必要开展研究以确定AF遗传风险是否可作为AF所致卒中的生物标志物。
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