Polygenic Risk for Depression Increases Risk of Ischemic Stroke: From the Stroke Genetics Network Study

Sylvia Wassertheil-Smoller; Qibin Qi; Tushar Dave; Braxton D Mitchell; Rebecca D Jackson; Simin Liu; Ki Park; Joel Salinas; Erin C Dunn; Enrique C Leira; Huichun Xu; Kathleen Ryan; Jordan W Smoller

doi:10.1161/STROKEAHA.117.018857

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Polygenic Risk for Depression Increases Risk of Ischemic Stroke: From the Stroke Genetics Network Study

Journal article

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Polygenic Risk for Depression Increases Risk of Ischemic Stroke: From the Stroke Genetics Network Study

Sylvia Wassertheil-Smoller, Qibin Qi, Tushar Dave, Braxton D Mitchell, Rebecca D Jackson, Simin Liu, Ki Park, Joel Salinas, Erin C Dunn, Enrique C Leira, …

Stroke (1970), Vol.49(3), pp.543-548

03/2018

DOI: 10.1161/STROKEAHA.117.018857

PMCID: PMC5909718

PMID: 29438084

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Abstract

Although depression is a risk factor for stroke in large prospective studies, it is unknown whether these conditions have a shared genetic basis.\nWe 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.\nThe depression PRS was associated with higher risk of ischemic stroke overall in both European (\n=0.025) and African ancestry (\n=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.\nHigher 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.

European Continental Ancestry Group - genetics

Genome-Wide Association Study

Humans

Middle Aged

Risk Factors

Stroke - complications

Male

Depression - genetics

Depression - ethnology

Multifactorial Inheritance

Stroke - genetics

Depression - etiology

Aged, 80 and over

Stroke - ethnology

Female

Aged

African Continental Ancestry Group - genetics

Details

Title: Subtitle: Polygenic Risk for Depression Increases Risk of Ischemic Stroke: From the Stroke Genetics Network Study
Creators: Sylvia Wassertheil-Smoller - 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. sylvia.smoller@einstein.yu.edu
Qibin Qi - 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
Tushar Dave - 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
Braxton D Mitchell - 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
Rebecca D Jackson - 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
Simin Liu - 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
Ki Park - 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
Joel Salinas - 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
Erin C Dunn - 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
Enrique C Leira - 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
Huichun Xu - 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
Kathleen Ryan - 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
Jordan W Smoller - 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
Resource Type: Journal article
Publication Details: Stroke (1970), Vol.49(3), pp.543-548
DOI: 10.1161/STROKEAHA.117.018857
PMID: 29438084
PMCID: PMC5909718
NLM abbreviation: Stroke
ISSN: 0039-2499
eISSN: 1524-4628
Publisher: United States
Grant note: HHSN268201600018C / NHLBI NIH HHS\nN01 WH042119 / WHI NIH HHS\nHHSN268201600003C / NHLBI NIH HHS\nHHSN268201600004C / NHLBI NIH HHS\nHHSN268201600002C / NHLBI NIH HHS\nT32 NS048005 / NINDS NIH HHS\nR01 NS042618 / NINDS NIH HHS\nHHSN268201600001C / NHLBI NIH HHS\nR01 NS100178 / NINDS NIH HHS\nU01 NS069208 / NINDS NIH HHS\nK01 MH102403 / NIMH NIH HHS
Language: English
Date published: 03/2018
Academic Unit: Neurology; Epidemiology; Iowa Neuroscience Institute; Neurosurgery
Record Identifier: 9984070344702771

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