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The transcriptional landscape of age in human peripheral blood.

Authors: Marjolein J Peters|||Roby Joehanes|||Luke C Pilling|||Claudia Schurmann|||Karen N Conneely|||Joseph Powell|||Eva Reinmaa|||George L Sutphin|||Alexandra Zhernakova|||Katharina Schramm|||Yana A Wilson|||Sayuko Kobes|||Taru Tukiainen||| |||Yolande F Ramos|||Harald H H Göring|||Myriam Fornage|||Yongmei Liu|||Sina A Gharib|||Barbara E Stranger|||Philip L De Jager|||Abraham Aviv|||Daniel Levy|||Joanne M Murabito|||Peter J Munson|||Tianxiao Huan|||Albert Hofman|||André G Uitterlinden|||Fernando Rivadeneira|||Jeroen van Rooij|||Lisette Stolk|||Linda Broer|||Michael M P J Verbiest|||Mila Jhamai|||Pascal Arp|||Andres Metspalu|||Liina Tserel|||Lili Milani|||Nilesh J Samani|||Pärt Peterson|||Silva Kasela|||Veryan Codd|||Annette Peters|||Cavin K Ward-Caviness|||Christian Herder|||Melanie Waldenberger|||Michael Roden|||Paula Singmann|||Sonja Zeilinger|||Thomas Illig|||Georg Homuth|||Hans-Jörgen Grabe|||Henry Völzke|||Leif Steil|||Thomas Kocher|||Anna Murray|||David Melzer|||Hanieh Yaghootkar|||Stefania Bandinelli|||Eric K Moses|||Jack W Kent|||Joanne E Curran|||Matthew P Johnson|||Sarah Williams-Blangero|||Harm-Jan Westra|||Allan F McRae|||Jennifer A Smith|||Sharon L R Kardia|||Iiris Hovatta|||Markus Perola|||Samuli Ripatti|||Veikko Salomaa|||Anjali K Henders|||Nicholas G Martin|||Alicia K Smith|||Divya Mehta|||Elisabeth B Binder|||K Maria Nylocks|||Elizabeth M Kennedy|||Torsten Klengel|||Jingzhong Ding|||Astrid M Suchy-Dicey|||Daniel A Enquobahrie|||Jennifer Brody|||Jerome I Rotter|||Yii-Der I Chen|||Jeanine Houwing-Duistermaat|||Margreet Kloppenburg|||P Eline Slagboom|||Quinta Helmer|||Wouter den Hollander|||Shannon Bean|||Towfique Raj|||Noman Bakhshi|||Qiao Ping Wang|||Lisa J Oyston|||Bruce M Psaty|||Russell P Tracy|||Grant W Montgomery|||Stephen T Turner|||John Blangero|||Ingrid Meulenbelt|||Kerry J Ressler|||Jian Yang|||Lude Franke|||Johannes Kettunen|||Peter M Visscher|||G Gregory Neely|||Ron Korstanje|||Robert L Hanson|||Holger Prokisch|||Luigi Ferrucci|||Tonu Esko|||Alexander Teumer|||Joyce B J van Meurs|||Andrew D Johnson

Journal: Nature communications

Publication Type: Journal Article

Date: 2015

DOI: PMC4639797

ID: 26490707

Affiliations:

Affiliations

    Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.|||The National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702, USA.|||Epidemiology and Public Health, University of Exeter Medical School, Exeter EX4 1DB, UK.|||Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17493, Germany.|||Department of Human Genetics, School of Medicine, Emory University, Atlanta, Georgia 30301, USA.|||Centre for Neurogenetics and Statistical Genomics, Queensland Brain Institute, University of Queensland, St Lucia, Brisbane, Queensland 4000, Australia.|||Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.|||Nathan Shock Center of Excellence in the Basic Biology of Aging, The Jackson Laboratory, Bar Harbor, Maine 04609, USA.|||Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9700RB, The Netherlands.|||Institute of Human Genetics, Helmholz Zentrum München - German Research Center for Environmental Health, Neuherberg 85764, Germany.|||Neuroscience Division, Garvan Institute of Medical Research, Australia and Charles Perkins Centre and School of Molecular Bioscience, The University of Sydney, Sydney, New South Wales 2006, Australia.|||Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Phoenix, Arizona 85001, USA.|||Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki 00131, Finland.||||||Department of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.|||Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.|||Division of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Sciences, Center at Houston, Texas 77001, USA.|||Department of Epidemiology and Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27101, USA.|||Computational Medicine Core, Center for Lung Biology, University of Washington, Seattle, Washington 98101, USA.|||Section of Genetic Medicine, Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois 60290, USA.|||Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02108, USA.|||Center of Human Development and Aging, New Jersey Medical School, Newark 07101, USA.|||The National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702, USA.|||The National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702, USA.|||The Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20817, USA.|||The National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702, USA.|||Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000CA, The Netherlands.|||Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.|||Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.|||Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.|||Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.|||Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.|||Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.|||Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.|||Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.|||Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.|||Molecular Pathology, Institute of Biomedicine, University of Tartu, Tartu 0794, Estonia.|||Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.|||Department of Cardiovascular Sciences, University of Leicester, Leicester LE1, UK.|||Molecular Pathology, Institute of Biomedicine, University of Tartu, Tartu 0794, Estonia.|||Institute of Molecular and Cell Biology, Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.|||Department of Cardiovascular Sciences, University of Leicester, Leicester LE1, UK.|||Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.|||Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.|||Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf 40593, Germany.|||Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.|||Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf 40593, Germany.|||Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.|||Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.|||Hannover Unified Biobank, Hannover Medical School, Hannover 30519, Germany.|||Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17493, Germany.|||Department of Psychiatry and Psychotherapy, Helios Hospital Stralsund, University Medicine Greifswald, Greifswald 17489, Germany.|||Institute for Community Medicine, University Medicine Greifswald, Greifswald 17489, Germany.|||Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17493, Germany.|||Unit of Periodontology, Department of Restorative Dentistry, Periodontology and Endodontology, University Medicine Greifswald, Greifswald 17489, Germany.|||Epidemiology and Public Health, University of Exeter Medical School, Exeter EX4 1DB, UK.|||Epidemiology and Public Health, University of Exeter Medical School, Exeter EX4 1DB, UK.|||Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.|||Geriatric Unit, Azienda Sanitaria di Firenze, Florence 50123, Italy.|||Centre for Genetic Origins of Health and Disease, The University of Western Australia, and Faculty of Health Sciences, Curtin University, Perth, Western Australia 9011, Australia.|||Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.|||Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.|||Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.|||Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.|||Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9700RB, The Netherlands.|||The Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4000, Australia.|||Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48103, USA.|||Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48103, USA.|||Department of Biosciences, University of Helsinki, Helsinki 00100, Finland.|||Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.|||Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki 00131, Finland.|||Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki 00131, Finland.|||The Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4000, Australia.|||QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4000, Australia.|||Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30301, USA.|||Max-Planck Institute of Psychiatry, Munich 80331, Germany.|||Max-Planck Institute of Psychiatry, Munich 80331, Germany.|||Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30301, USA.|||Department of Human Genetics, School of Medicine, Emory University, Atlanta, Georgia 30301, USA.|||Max-Planck Institute of Psychiatry, Munich 80331, Germany.|||Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 27101, USA.|||Department of Epidemiology, University of Washington, Seattle, Washington 98101, USA.|||Department of Epidemiology, University of Washington, Seattle, Washington 98101, USA.|||Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98101, USA.|||Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90501, USA.|||Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90501, USA.|||Department of Medical Statistics, Leiden University Medical Center, Leiden 2300RC, The Netherlands.|||Department of Rheumatology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.|||Department of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.|||Department of Medical Statistics, Leiden University Medical Center, Leiden 2300RC, The Netherlands.|||Department of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.|||Nathan Shock Center of Excellence in the Basic Biology of Aging, The Jackson Laboratory, Bar Harbor, Maine 04609, USA.|||Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02138, USA.|||Neuroscience Division, Garvan Institute of Medical Research, Australia and Charles Perkins Centre and School of Molecular Bioscience, The University of Sydney, Sydney, New South Wales 2006, Australia.|||Neuroscience Division, Garvan Institute of Medical Research, Australia and Charles Perkins Centre and School of Molecular Bioscience, The University of Sydney, Sydney, New South Wales 2006, Australia.|||Neuroscience Division, Garvan Institute of Medical Research, Australia and Charles Perkins Centre and School of Molecular Bioscience, The University of Sydney, Sydney, New South Wales 2006, Australia.|||Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98195, USA.|||Department of Pathology, University of Vermont College of Medicine, Colchester, Vermont 98195, USA.|||QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4000, Australia.|||Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota 55901, USA.|||Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.|||Department of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.|||Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30301, USA.|||The Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4000, Australia.|||Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9700RB, The Netherlands.|||Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki 00131, Finland.|||The Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4000, Australia.|||Neuroscience Division, Garvan Institute of Medical Research, Australia and Charles Perkins Centre and School of Molecular Bioscience, The University of Sydney, Sydney, New South Wales 2006, Australia.|||Nathan Shock Center of Excellence in the Basic Biology of Aging, The Jackson Laboratory, Bar Harbor, Maine 04609, USA.|||Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Phoenix, Arizona 85001, USA.|||Institute of Human Genetics, Helmholz Zentrum München - German Research Center for Environmental Health, Neuherberg 85764, Germany.|||Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 21218, USA.|||Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.|||Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17493, Germany.|||Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.|||The National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702, USA.

Abstract

Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.

Chemical List

    Biomarkers

Reference List

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