February 23, 2021; 96 (8) ArticleOpen Access
Association of Circulating Metabolites in Plasma or Serum and Risk of Stroke
Meta-analysis From 7 Prospective Cohorts
Dina Vojinovic, Marita Kalaoja, Stella Trompet, Krista Fischer, Martin J. Shipley, View ORCID ProfileShuo Li, Aki S. Havulinna, Markus Perola, Veikko Salomaa, Qiong Yang, Naveed Sattar, Pekka Jousilahti, Najaf Amin, View ORCID ProfileClaudia L. Satizabal, Nele Taba, View ORCID ProfileBehnam Sabayan, Ramachandran S. Vasan, M. Arfan Ikram, David J. Stott, View ORCID ProfileMika Ala-Korpela, J. Wouter Jukema, Sudha Seshadri, Johannes Kettunen, View ORCID ProfileMika Kivimaki, Tonu Esko, Cornelia M. van Duijn
First published December 2, 2020, DOI: https://doi.org/10.1212/WNL.0000000000011236
Dina Vojinovic
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Marita Kalaoja
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Stella Trompet
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Krista Fischer
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Martin J. Shipley
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Shuo Li
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Aki S. Havulinna
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Markus Perola
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Veikko Salomaa
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Qiong Yang
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Naveed Sattar
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Pekka Jousilahti
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Najaf Amin
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Claudia L. Satizabal
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Nele Taba
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Behnam Sabayan
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Ramachandran S. Vasan
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
M. Arfan Ikram
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
David J. Stott
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Mika Ala-Korpela
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
J. Wouter Jukema
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Sudha Seshadri
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Johannes Kettunen
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Mika Kivimaki
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Tonu Esko
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Cornelia M. van Duijn
From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.
Association of Circulating Metabolites in Plasma or Serum and Risk of Stroke
Meta-analysis From 7 Prospective Cohorts
Dina Vojinovic, Marita Kalaoja, Stella Trompet, Krista Fischer, Martin J. Shipley, Shuo Li, Aki S. Havulinna, Markus Perola, Veikko Salomaa, Qiong Yang, Naveed Sattar, Pekka Jousilahti, Najaf Amin, Claudia L. Satizabal, Nele Taba, Behnam Sabayan, Ramachandran S. Vasan, M. Arfan Ikram, David J. Stott, Mika Ala-Korpela, J. Wouter Jukema, Sudha Seshadri, Johannes Kettunen, Mika Kivimaki, Tonu Esko, Cornelia M. van Duijn
Neurology Feb 2021, 96 (8) e1110-e1123; DOI: 10.1212/WNL.0000000000011236
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Abstract
Objective To conduct a comprehensive analysis of circulating metabolites and incident stroke in large prospective population-based settings.
Methods We investigated the association of metabolites with risk of stroke in 7 prospective cohort studies including 1,791 incident stroke events among 38,797 participants in whom circulating metabolites were measured by nuclear magnetic resonance technology. The relationship between metabolites and stroke was assessed with Cox proportional hazards regression models. The analyses were performed considering all incident stroke events and ischemic and hemorrhagic events separately.
Results The analyses revealed 10 significant metabolite associations. Amino acid histidine (hazard ratio [HR] per SD 0.90, 95% confidence interval [CI] 0.85, 0.94; p = 4.45 × 10−5), glycolysis-related metabolite pyruvate (HR per SD 1.09, 95% CI 1.04, 1.14; p = 7.45 × 10−4), acute-phase reaction marker glycoprotein acetyls (HR per SD 1.09, 95% CI 1.03, 1.15; p = 1.27 × 10−3), cholesterol in high-density lipoprotein (HDL) 2, and several other lipoprotein particles were associated with risk of stroke. When focused on incident ischemic stroke, a significant association was observed with phenylalanine (HR per SD 1.12, 95% CI 1.05, 1.19; p = 4.13 × 10−4) and total and free cholesterol in large HDL particles.
Conclusions We found association of amino acids, glycolysis-related metabolites, acute-phase reaction markers, and several lipoprotein subfractions with the risk of stroke. These findings support the potential of metabolomics to provide new insights into the metabolic changes preceding stroke.
Glossary
- BMI=
- body mass index;
- CI=
- confidence interval;
- DILGOM=
- Dietary, Lifestyle and Genetic Determinants of Obesity and Metabolic Syndrome;
- EGCUT=
- Estonian biobank;
- FHS=
- Framingham Heart Study;
- FINRISK97=
- FINRISK study 1997;
- HDL=
- high-density lipoprotein;
- HR=
- hazard ratio;
- ICD=
- International Classification of Diseases;
- LDL=
- low-density lipoprotein;
- NMR=
- nuclear magnetic resonance;
- PROSPER=
- Prospective Study of Pravastatin in the Elderly at Risk
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
The Article Processing charge will be funded by Erasmus Medical Center.
- Received July 13, 2019.
- Accepted in final form October 28, 2020.
- Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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