Wassertheil-Smoller Sylvia, Qi Qibin, Dave Tushar, Mitchell Braxton D, Jackson Rebecca D, Liu Simin, Park Ki, Salinas Joel, Dunn Erin C, Leira Enrique C, Xu Huichun, Ryan Kathleen, Smoller Jordan W
From the Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (S.W.-S., Q.Q.); University of Maryland School of Medicine, Baltimore (T.D., B.D.M., H.X., K.R.); Department of Medicine, Ohio State University, Columbus (R.D.J.); Department of Epidemiology (S.L.) and Department of Medicine (S.L.), Brown School of Public Health and Alpert Medical School, Providence, RI; Division of Cardiology, University of Florida, Gainesville (K.P.); Department of Neurology (J.S.) and Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Center for Genomic Medicine (E.C.D., J.W.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Neurology, Carver College of Medicine (E.C.L.) and Department of Epidemiology, College of Public Health (E.C.L.), University of Iowa, Iowa City.
Stroke. 2018 Mar;49(3):543-548. doi: 10.1161/STROKEAHA.117.018857. Epub 2018 Feb 8.
Although depression is a risk factor for stroke in large prospective studies, it is unknown whether these conditions have a shared genetic basis.
We applied a polygenic risk score (PRS) for major depressive disorder derived from European ancestry analyses by the Psychiatric Genomics Consortium to a genome-wide association study of ischemic stroke in the Stroke Genetics Network of National Institute of Neurological Disorders and Stroke. Included in separate analyses were 12 577 stroke cases and 25 643 controls of European ancestry and 1353 cases and 2383 controls of African ancestry. We examined the association between depression PRS and ischemic stroke overall and with pathogenic subtypes using logistic regression analyses.
The depression PRS was associated with higher risk of ischemic stroke overall in both European (=0.025) and African ancestry (=0.011) samples from the Stroke Genetics Network. Ischemic stroke risk increased by 3.0% (odds ratio, 1.03; 95% confidence interval, 1.00-1.05) for every 1 SD increase in PRS for those of European ancestry and by 8% (odds ratio, 1.08; 95% confidence interval, 1.04-1.13) for those of African ancestry. Among stroke subtypes, elevated risk of small artery occlusion was observed in both European and African ancestry samples. Depression PRS was also associated with higher risk of cardioembolic stroke in European ancestry and large artery atherosclerosis in African ancestry persons.
Higher polygenic risk for major depressive disorder is associated with increased risk of ischemic stroke overall and with small artery occlusion. Additional associations with ischemic stroke subtypes differed by ancestry.
尽管在大型前瞻性研究中抑郁症是中风的一个风险因素，但尚不清楚这两种疾病是否具有共同的遗传基础。
我们将精神疾病基因组学联盟基于欧洲血统分析得出的重度抑郁症多基因风险评分（PRS）应用于美国国立神经疾病与中风研究所中风遗传学网络的缺血性中风全基因组关联研究。单独分析纳入了12577例欧洲血统的中风病例和25643例对照，以及1353例非洲血统的病例和2383例对照。我们使用逻辑回归分析研究了抑郁症PRS与总体缺血性中风以及与致病性亚型之间的关联。
在中风遗传学网络的欧洲血统（P=0.025）和非洲血统（P=0.011）样本中，抑郁症PRS与总体缺血性中风风险较高相关。对于欧洲血统的人，PRS每增加1个标准差，缺血性中风风险增加3.0%（优势比，1.03；95%置信区间，1.00 - 1.05）；对于非洲血统的人，风险增加8%（优势比，1.08；95%置信区间，1.04 - 1.13）。在中风亚型中，欧洲和非洲血统样本中均观察到小动脉闭塞风险升高。抑郁症PRS在欧洲血统人群中还与心源性栓塞性中风风险较高相关，在非洲血统人群中与大动脉粥样硬化风险较高相关。
重度抑郁症较高的多基因风险与总体缺血性中风风险增加以及小动脉闭塞相关。与缺血性中风亚型的其他关联因血统而异。
