title: Polygenic risk of ischemic stroke is associated with cognitive ability.
abstract: OBJECTIVE
  We investigated the correlation between polygenic risk of ischemic stroke (and its subtypes) and cognitive ability in 3 relatively healthy Scottish cohorts: the Lothian Birth Cohort 1936 (LBC1936), the Lothian Birth Cohort 1921 (LBC1921), and Generation Scotland: Scottish Family Health Study (GS).
  
  
  METHODS
  Polygenic risk scores for ischemic stroke were created in LBC1936 (n = 1005), LBC1921 (n = 517), and GS (n = 6,815) using genome-wide association study summary data from the METASTROKE collaboration. We investigated whether the polygenic risk scores correlate with cognitive ability in the 3 cohorts.
  
  
  RESULTS
  In the largest cohort, GS, polygenic risk of all ischemic stroke, small vessel disease stroke, and large vessel disease stroke, but not cardioembolic stroke, were correlated with both fluid and crystallized cognitive abilities. The highest correlation was between a polygenic risk score for all ischemic stroke and general cognitive ability (r = -0.070, p = 1.95 × 10(-8)). Few correlations were identified in LBC1936 and LBC1921, but a meta-analysis of all 3 cohorts supported the correlation between polygenic risk of ischemic stroke and cognitive ability.
  
  
  CONCLUSIONS
  The findings from this study indicate that even in the absence of stroke, being at high polygenic risk of ischemic stroke is associated with lower cognitive ability.
authors.affiliation: From the Centre for Cognitive Ageing and Cognitive Epidemiology (S.E.H., R. Marioni, C.L.M.S., M.E.B., J.M.S., D.J.P., J.M.W., I.J.D.), Centre for Clinical Brain Sciences (C.L.M.S., M.E.B., J.M.W.), Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), Alzheimer Scotland Dementia Research Centre (J.M.S.), and Department of Psychology (I.J.D.), University of Edinburgh; Medical Genetics Section (S.E.H., R. Marioni, A.C., C.L.M.S., D.J.P.), University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK; Institute for Stroke and Dementia Research (R. Malik), Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; Queensland Brain Institute (R. Marioni), The University of Queensland, Brisbane, Australia; Department of Neurology (S.S.), Boston University School of Medicine, Framingham; The Framingham Heart Study (S.S.), Framingham, MA; and Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville. Sarah.Harris@igmm.ed.ac.uk.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Harris
authors.affiliation: From the Centre for Cognitive Ageing and Cognitive Epidemiology (S.E.H., R. Marioni, C.L.M.S., M.E.B., J.M.S., D.J.P., J.M.W., I.J.D.), Centre for Clinical Brain Sciences (C.L.M.S., M.E.B., J.M.W.), Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), Alzheimer Scotland Dementia Research Centre (J.M.S.), and Department of Psychology (I.J.D.), University of Edinburgh; Medical Genetics Section (S.E.H., R. Marioni, A.C., C.L.M.S., D.J.P.), University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK; Institute for Stroke and Dementia Research (R. Malik), Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; Queensland Brain Institute (R. Marioni), The University of Queensland, Brisbane, Australia; Department of Neurology (S.S.), Boston University School of Medicine, Framingham; The Framingham Heart Study (S.S.), Framingham, MA; and Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville.
authors.forename: Rainer
authors.initials: R
authors.lastname: Malik
authors.affiliation: From the Centre for Cognitive Ageing and Cognitive Epidemiology (S.E.H., R. Marioni, C.L.M.S., M.E.B., J.M.S., D.J.P., J.M.W., I.J.D.), Centre for Clinical Brain Sciences (C.L.M.S., M.E.B., J.M.W.), Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), Alzheimer Scotland Dementia Research Centre (J.M.S.), and Department of Psychology (I.J.D.), University of Edinburgh; Medical Genetics Section (S.E.H., R. Marioni, A.C., C.L.M.S., D.J.P.), University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK; Institute for Stroke and Dementia Research (R. Malik), Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; Queensland Brain Institute (R. Marioni), The University of Queensland, Brisbane, Australia; Department of Neurology (S.S.), Boston University School of Medicine, Framingham; The Framingham Heart Study (S.S.), Framingham, MA; and Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Marioni
authors.affiliation: From the Centre for Cognitive Ageing and Cognitive Epidemiology (S.E.H., R. Marioni, C.L.M.S., M.E.B., J.M.S., D.J.P., J.M.W., I.J.D.), Centre for Clinical Brain Sciences (C.L.M.S., M.E.B., J.M.W.), Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), Alzheimer Scotland Dementia Research Centre (J.M.S.), and Department of Psychology (I.J.D.), University of Edinburgh; Medical Genetics Section (S.E.H., R. Marioni, A.C., C.L.M.S., D.J.P.), University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK; Institute for Stroke and Dementia Research (R. Malik), Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; Queensland Brain Institute (R. Marioni), The University of Queensland, Brisbane, Australia; Department of Neurology (S.S.), Boston University School of Medicine, Framingham; The Framingham Heart Study (S.S.), Framingham, MA; and Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville.
authors.forename: Archie
authors.initials: A
authors.lastname: Campbell
authors.affiliation: From the Centre for Cognitive Ageing and Cognitive Epidemiology (S.E.H., R. Marioni, C.L.M.S., M.E.B., J.M.S., D.J.P., J.M.W., I.J.D.), Centre for Clinical Brain Sciences (C.L.M.S., M.E.B., J.M.W.), Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), Alzheimer Scotland Dementia Research Centre (J.M.S.), and Department of Psychology (I.J.D.), University of Edinburgh; Medical Genetics Section (S.E.H., R. Marioni, A.C., C.L.M.S., D.J.P.), University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK; Institute for Stroke and Dementia Research (R. Malik), Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; Queensland Brain Institute (R. Marioni), The University of Queensland, Brisbane, Australia; Department of Neurology (S.S.), Boston University School of Medicine, Framingham; The Framingham Heart Study (S.S.), Framingham, MA; and Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.affiliation: From the Centre for Cognitive Ageing and Cognitive Epidemiology (S.E.H., R. Marioni, C.L.M.S., M.E.B., J.M.S., D.J.P., J.M.W., I.J.D.), Centre for Clinical Brain Sciences (C.L.M.S., M.E.B., J.M.W.), Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), Alzheimer Scotland Dementia Research Centre (J.M.S.), and Department of Psychology (I.J.D.), University of Edinburgh; Medical Genetics Section (S.E.H., R. Marioni, A.C., C.L.M.S., D.J.P.), University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK; Institute for Stroke and Dementia Research (R. Malik), Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; Queensland Brain Institute (R. Marioni), The University of Queensland, Brisbane, Australia; Department of Neurology (S.S.), Boston University School of Medicine, Framingham; The Framingham Heart Study (S.S.), Framingham, MA; and Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville.
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Worrall
authors.affiliation: From the Centre for Cognitive Ageing and Cognitive Epidemiology (S.E.H., R. Marioni, C.L.M.S., M.E.B., J.M.S., D.J.P., J.M.W., I.J.D.), Centre for Clinical Brain Sciences (C.L.M.S., M.E.B., J.M.W.), Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), Alzheimer Scotland Dementia Research Centre (J.M.S.), and Department of Psychology (I.J.D.), University of Edinburgh; Medical Genetics Section (S.E.H., R. Marioni, A.C., C.L.M.S., D.J.P.), University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK; Institute for Stroke and Dementia Research (R. Malik), Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; Queensland Brain Institute (R. Marioni), The University of Queensland, Brisbane, Australia; Department of Neurology (S.S.), Boston University School of Medicine, Framingham; The Framingham Heart Study (S.S.), Framingham, MA; and Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville.
authors.forename: Cathie L M
authors.initials: CL
authors.lastname: Sudlow
authors.affiliation: From the Centre for Cognitive Ageing and Cognitive Epidemiology (S.E.H., R. Marioni, C.L.M.S., M.E.B., J.M.S., D.J.P., J.M.W., I.J.D.), Centre for Clinical Brain Sciences (C.L.M.S., M.E.B., J.M.W.), Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), Alzheimer Scotland Dementia Research Centre (J.M.S.), and Department of Psychology (I.J.D.), University of Edinburgh; Medical Genetics Section (S.E.H., R. Marioni, A.C., C.L.M.S., D.J.P.), University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK; Institute for Stroke and Dementia Research (R. Malik), Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; Queensland Brain Institute (R. Marioni), The University of Queensland, Brisbane, Australia; Department of Neurology (S.S.), Boston University School of Medicine, Framingham; The Framingham Heart Study (S.S.), Framingham, MA; and Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.affiliation: From the Centre for Cognitive Ageing and Cognitive Epidemiology (S.E.H., R. Marioni, C.L.M.S., M.E.B., J.M.S., D.J.P., J.M.W., I.J.D.), Centre for Clinical Brain Sciences (C.L.M.S., M.E.B., J.M.W.), Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), Alzheimer Scotland Dementia Research Centre (J.M.S.), and Department of Psychology (I.J.D.), University of Edinburgh; Medical Genetics Section (S.E.H., R. Marioni, A.C., C.L.M.S., D.J.P.), University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK; Institute for Stroke and Dementia Research (R. Malik), Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; Queensland Brain Institute (R. Marioni), The University of Queensland, Brisbane, Australia; Department of Neurology (S.S.), Boston University School of Medicine, Framingham; The Framingham Heart Study (S.S.), Framingham, MA; and Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Bastin
authors.affiliation: From the Centre for Cognitive Ageing and Cognitive Epidemiology (S.E.H., R. Marioni, C.L.M.S., M.E.B., J.M.S., D.J.P., J.M.W., I.J.D.), Centre for Clinical Brain Sciences (C.L.M.S., M.E.B., J.M.W.), Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), Alzheimer Scotland Dementia Research Centre (J.M.S.), and Department of Psychology (I.J.D.), University of Edinburgh; Medical Genetics Section (S.E.H., R. Marioni, A.C., C.L.M.S., D.J.P.), University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK; Institute for Stroke and Dementia Research (R. Malik), Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; Queensland Brain Institute (R. Marioni), The University of Queensland, Brisbane, Australia; Department of Neurology (S.S.), Boston University School of Medicine, Framingham; The Framingham Heart Study (S.S.), Framingham, MA; and Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville.
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
authors.affiliation: From the Centre for Cognitive Ageing and Cognitive Epidemiology (S.E.H., R. Marioni, C.L.M.S., M.E.B., J.M.S., D.J.P., J.M.W., I.J.D.), Centre for Clinical Brain Sciences (C.L.M.S., M.E.B., J.M.W.), Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), Alzheimer Scotland Dementia Research Centre (J.M.S.), and Department of Psychology (I.J.D.), University of Edinburgh; Medical Genetics Section (S.E.H., R. Marioni, A.C., C.L.M.S., D.J.P.), University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK; Institute for Stroke and Dementia Research (R. Malik), Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; Queensland Brain Institute (R. Marioni), The University of Queensland, Brisbane, Australia; Department of Neurology (S.S.), Boston University School of Medicine, Framingham; The Framingham Heart Study (S.S.), Framingham, MA; and Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville.
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.affiliation: From the Centre for Cognitive Ageing and Cognitive Epidemiology (S.E.H., R. Marioni, C.L.M.S., M.E.B., J.M.S., D.J.P., J.M.W., I.J.D.), Centre for Clinical Brain Sciences (C.L.M.S., M.E.B., J.M.W.), Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), Alzheimer Scotland Dementia Research Centre (J.M.S.), and Department of Psychology (I.J.D.), University of Edinburgh; Medical Genetics Section (S.E.H., R. Marioni, A.C., C.L.M.S., D.J.P.), University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK; Institute for Stroke and Dementia Research (R. Malik), Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; Queensland Brain Institute (R. Marioni), The University of Queensland, Brisbane, Australia; Department of Neurology (S.S.), Boston University School of Medicine, Framingham; The Framingham Heart Study (S.S.), Framingham, MA; and Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardlaw
authors.affiliation: From the Centre for Cognitive Ageing and Cognitive Epidemiology (S.E.H., R. Marioni, C.L.M.S., M.E.B., J.M.S., D.J.P., J.M.W., I.J.D.), Centre for Clinical Brain Sciences (C.L.M.S., M.E.B., J.M.W.), Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), Alzheimer Scotland Dementia Research Centre (J.M.S.), and Department of Psychology (I.J.D.), University of Edinburgh; Medical Genetics Section (S.E.H., R. Marioni, A.C., C.L.M.S., D.J.P.), University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK; Institute for Stroke and Dementia Research (R. Malik), Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; Queensland Brain Institute (R. Marioni), The University of Queensland, Brisbane, Australia; Department of Neurology (S.S.), Boston University School of Medicine, Framingham; The Framingham Heart Study (S.S.), Framingham, MA; and Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D002648:Child; D003071:Cognition; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D012606:Scotland / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D055815:Young Adult