title: Genetic overlap between diagnostic subtypes of ischemic stroke.
abstract: OBJECTIVE
  Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses.
  
  
  METHODS
  Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles.
  
  
  RESULTS
  High genetic correlation was identified between LAA and SVD using linear mixed models (rg=0.96, SE=0.47, P=9×10(-4)) and profile scores (rg=0.72; 95% confidence interval, 0.52-0.93). Between LAA and cardioembolism and SVD and cardioembolism, correlation was moderate using linear mixed models but not significantly different from zero for profile scoring. Joint meta-analysis of LAA and SVD identified strong association (P=1×10(-7)) for single nucleotide polymorphisms near the opioid receptor μ1 (OPRM1) gene.
  
  
  CONCLUSIONS
  Our results suggest that LAA and SVD, which have been hitherto treated as genetically distinct, may share a substantial genetic component. Combined analyses of LAA and SVD may increase power to identify small-effect alleles influencing shared pathophysiological processes.
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Holliday
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Matthew
authors.initials: M
authors.lastname: Traylor
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Rainer
authors.initials: R
authors.lastname: Malik
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Steve
authors.initials: S
authors.lastname: Bevan
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Guido
authors.initials: G
authors.lastname: Falcone
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Jemma C
authors.initials: JC
authors.lastname: Hopewell
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Cheng
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Ioana
authors.initials: I
authors.lastname: Cotlarciuc
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Bis
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Giorgio B
authors.initials: GB
authors.lastname: Boncoraglio
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Robert
authors.initials: R
authors.lastname: Clarke
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: John W
authors.initials: JW
authors.lastname: Cole
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Karen L
authors.initials: KL
authors.lastname: Furie
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Jim
authors.initials: J
authors.lastname: Jannes
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kittner
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Lincz
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Jane M
authors.initials: JM
authors.lastname: Maguire
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: James F
authors.initials: JF
authors.lastname: Meschia
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Mike A
authors.initials: MA
authors.lastname: Nalls
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Christopher
authors.initials: C
authors.lastname: Oldmeadow
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Eugenio A
authors.initials: EA
authors.lastname: Parati
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Peter M
authors.initials: PM
authors.lastname: Rothwell
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Pankaj
authors.initials: P
authors.lastname: Sharma
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Cathie
authors.initials: C
authors.lastname: Sudlow
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Kerri L
authors.initials: KL
authors.lastname: Wiggins
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Worrall
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Markus
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Christopher
authors.initials: C
authors.lastname: Levi
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: John
authors.initials: J
authors.lastname: Attia
authors.affiliation: From the School of Medicine and Public Health (E.G.H., J.A.), School of Biomedical Sciences and Pharmacy (L.F.L., R.J.S.), and School of Nursing and Midwifery (J.M.M.), University of Newcastle, Australia; Clinical Research Design, IT and Statistical Support Unit, Public Health Research Program, Hunter Medical Research Institute, Newcastle, Australia (E.G.H., C.O., J.A.); Department of Clinical Neurosciences, University of Cambridge, UK (M.T., S.B., H.S.M.); Institute for Stroke and Dementia Research, Klinikum der Universität Mün-chen, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (G.F., J.R.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (G.F., J.R.); Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., R.C.) and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), University of Oxford, UK; Department of Medicine (Y.-C.C., B.D.M.) and Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore, MD; Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College, London, UK (I.C.); Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P., K.L.W.) and Department of Epidemiology (B.M.P.), University of Washington, Seattle, WA; Institute of Molecular Medicine and Human Genetics Center, the University of Texas Health Science Center at Houston, TX (E.B., M.F.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.B., E.A.P.); Department of Neurology, Veterans Affairs Medical Center, Baltimore, MD (J.W.C., S.J.K.); Department of Neurology, Rhode Island Hospital, Providence, RI (K.L.F.); Departments of Epidemiology, Neurology, and Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands (M.A.I.); School of Medicine, University of Adelaide, Australia (J.J.); H
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Wray
mesh_terms: D000483:Alleles; D050197:Atherosclerosis / Q000175:diagnosis / Q000235:genetics*; D059345:Cerebral Small Vessel Diseases / Q000175:diagnosis / Q000235:genetics*; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D004617:Embolism / Q000175:diagnosis / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007511:Ischemia / Q000175:diagnosis / Q000235:genetics; D016014:Linear Models; D015201:Meta-Analysis as Topic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000175:diagnosis / Q000235:genetics*
keywords: atherosclerosis; genetic epidemiology; lacunar stroke