The transcriptional landscape of age in human peripheral blood

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 () and Andrew D. Johnson ()
Additional contact information
Marjolein J. Peters: Erasmus Medical Centre Rotterdam
Roby Joehanes: The National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study
Luke C. Pilling: Epidemiology and Public Health, University of Exeter Medical School
Claudia Schurmann: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald
Karen N. Conneely: School of Medicine, Emory University
Joseph Powell: Centre for Neurogenetics and Statistical Genomics, Queensland Brain Institute, University of Queensland
Eva Reinmaa: Estonian Genome Center, University of Tartu
George L. Sutphin: Nathan Shock Center of Excellence in the Basic Biology of Aging, The Jackson Laboratory
Alexandra Zhernakova: University Medical Center Groningen, University of Groningen
Katharina Schramm: Institute of Human Genetics, Helmholz Zentrum München - German Research Center for Environmental Health
Yana A. Wilson: Garvan Institute of Medical Research, Australia and Charles Perkins Centre and School of Molecular Bioscience, The University of Sydney
Sayuko Kobes: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health
Taru Tukiainen: Institute for Molecular Medicine Finland FIMM, University of Helsinki
Yolande F. Ramos: Leiden University Medical Center
Harald H. H. Göring: Texas Biomedical Research Institute
Myriam Fornage: Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Sciences
Yongmei Liu: Public Health Sciences, Wake Forest School of Medicine
Sina A. Gharib: Computational Medicine Core, Center for Lung Biology, University of Washington
Barbara E. Stranger: Section of Genetic Medicine, Institute for Genomics and Systems Biology, University of Chicago
Philip L. De Jager: Program in Translational NeuroPsychiatric Genomics, Brigham and Women’s Hospital, Harvard Medical School
Abraham Aviv: Center of Human Development and Aging, New Jersey Medical School
Daniel Levy: The National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study
Joanne M. Murabito: The National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study
Peter J. Munson: The Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health
Tianxiao Huan: The National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study
Albert Hofman: Erasmus Medical Center
André G. Uitterlinden: Erasmus Medical Centre Rotterdam
Fernando Rivadeneira: Erasmus Medical Centre Rotterdam
Jeroen van Rooij: Erasmus Medical Centre Rotterdam
Lisette Stolk: Erasmus Medical Centre Rotterdam
Linda Broer: Erasmus Medical Centre Rotterdam
Michael M. P. J. Verbiest: Erasmus Medical Centre Rotterdam
Mila Jhamai: Erasmus Medical Centre Rotterdam
Pascal Arp: Erasmus Medical Centre Rotterdam
Andres Metspalu: Estonian Genome Center, University of Tartu
Liina Tserel: Molecular Pathology, Institute of Biomedicine, University of Tartu
Lili Milani: Estonian Genome Center, University of Tartu
Nilesh J. Samani: University of Leicester
Pärt Peterson: Molecular Pathology, Institute of Biomedicine, University of Tartu
Silva Kasela: Institute of Molecular and Cell Biology, Estonian Genome Center, University of Tartu
Veryan Codd: University of Leicester
Annette Peters: Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health
Cavin K. Ward-Caviness: Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health
Christian Herder: Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf
Melanie Waldenberger: Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health
Michael Roden: Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf
Paula Singmann: Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health
Sonja Zeilinger: Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health
Thomas Illig: Hannover Unified Biobank, Hannover Medical School
Georg Homuth: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald
Hans-Jörgen Grabe: Helios Hospital Stralsund, University Medicine Greifswald
Henry Völzke: Institute for Community Medicine, University Medicine Greifswald
Leif Steil: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald
Thomas Kocher: Unit of Periodontology, Periodontology and Endodontology, University Medicine Greifswald
Anna Murray: Epidemiology and Public Health, University of Exeter Medical School
David Melzer: Epidemiology and Public Health, University of Exeter Medical School
Hanieh Yaghootkar: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter
Stefania Bandinelli: Geriatric Unit, Azienda Sanitaria di Firenze
Eric K. Moses: Centre for Genetic Origins of Health and Disease, The University of Western Australia, and Faculty of Health Sciences, Curtin University
Jack W. Kent: Texas Biomedical Research Institute
Joanne E. Curran: Texas Biomedical Research Institute
Matthew P. Johnson: Texas Biomedical Research Institute
Sarah Williams-Blangero: Texas Biomedical Research Institute
Harm-Jan Westra: University Medical Center Groningen, University of Groningen
Allan F. McRae: The Queensland Brain Institute, University of Queensland
Jennifer A. Smith: University of Michigan
Sharon L. R. Kardia: University of Michigan
Iiris Hovatta: University of Helsinki
Markus Perola: Estonian Genome Center, University of Tartu
Samuli Ripatti: Institute for Molecular Medicine Finland FIMM, University of Helsinki
Veikko Salomaa: National Institute for Health and Welfare
Anjali K. Henders: The Institute for Molecular Bioscience, University of Queensland
Nicholas G. Martin: QIMR Berghofer Medical Research Institute
Alicia K. Smith: Emory University School of Medicine
Divya Mehta: Max-Planck Institute of Psychiatry
Elisabeth B. Binder: Max-Planck Institute of Psychiatry
K Maria Nylocks: Emory University School of Medicine
Elizabeth M. Kennedy: School of Medicine, Emory University
Torsten Klengel: Max-Planck Institute of Psychiatry
Jingzhong Ding: Wake Forest School of Medicine
Astrid M. Suchy-Dicey: University of Washington
Daniel A. Enquobahrie: University of Washington
Jennifer Brody: Cardiovascular Health Research Unit, University of Washington
Jerome I. Rotter: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Yii- Der I. Chen: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Jeanine Houwing-Duistermaat: Leiden University Medical Center
Margreet Kloppenburg: Leiden University Medical Center
P. Eline Slagboom: Leiden University Medical Center
Quinta Helmer: Leiden University Medical Center
Wouter den Hollander: Leiden University Medical Center
Shannon Bean: Nathan Shock Center of Excellence in the Basic Biology of Aging, The Jackson Laboratory
Towfique Raj: Harvard Medical School
Noman Bakhshi: Garvan Institute of Medical Research, Australia and Charles Perkins Centre and School of Molecular Bioscience, The University of Sydney
Qiao Ping Wang: Garvan Institute of Medical Research, Australia and Charles Perkins Centre and School of Molecular Bioscience, The University of Sydney
Lisa J. Oyston: Garvan Institute of Medical Research, Australia and Charles Perkins Centre and School of Molecular Bioscience, The University of Sydney
Bruce M. Psaty: Cardiovascular Health Research Unit, University of Washington
Russell P. Tracy: University of Vermont College of Medicine
Grant W. Montgomery: QIMR Berghofer Medical Research Institute
Stephen T. Turner: Mayo Clinic
John Blangero: Texas Biomedical Research Institute
Ingrid Meulenbelt: Leiden University Medical Center
Kerry J. Ressler: Emory University School of Medicine
Jian Yang: The Queensland Brain Institute, University of Queensland
Lude Franke: University Medical Center Groningen, University of Groningen
Johannes Kettunen: Institute for Molecular Medicine Finland FIMM, University of Helsinki
Peter M. Visscher: The Queensland Brain Institute, University of Queensland
G. Gregory Neely: Garvan Institute of Medical Research, Australia and Charles Perkins Centre and School of Molecular Bioscience, The University of Sydney
Ron Korstanje: Nathan Shock Center of Excellence in the Basic Biology of Aging, The Jackson Laboratory
Robert L. Hanson: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health
Holger Prokisch: Institute of Human Genetics, Helmholz Zentrum München - German Research Center for Environmental Health
Luigi Ferrucci: Clinical Research Branch, National Institute on Aging
Tonu Esko: Estonian Genome Center, University of Tartu
Alexander Teumer: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald
Joyce B. J. van Meurs: Erasmus Medical Centre Rotterdam
Andrew D. Johnson: The National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9570

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