The transcriptional landscape of age in human peripheral blood
Marjolein J. Peters(Erasmus University Rotterdam), Roby Joehanes(National Heart Lung and Blood Institute), Luke C. Pilling(University of Exeter), Claudia Schurmann(Universitätsmedizin Greifswald), Karen N. Conneely(Emory University), Joseph E. Powell(The University of Queensland), Eva Reinmaa(Estonian Biocentre), George L. Sutphin(Jackson Laboratory), Alexandra Zhernakova(University Medical Center Groningen), Katharina Schramm(Helmholtz Zentrum München), Yana A. Wilson(The University of Sydney), Sayuko Kobes(National Institutes of Health), Taru Tukiainen(University of Helsinki), Michael A. Nalls(National Institutes of Health), Dena Hernández(National Institutes of Health), Mark Cookson(National Institutes of Health), J. Raphael Gibbs(National Institutes of Health), John Hardy(National Hospital for Neurology and Neurosurgery), Adaikalavan Ramasamy(Guy's Hospital), Alan B. Zonderman(National Institutes of Health), Allissa Dillman(National Institutes of Health), Bryan J. Traynor(National Institutes of Health), Colin Smith(University of Edinburgh), Dan L. Longo(National Institutes of Health), Daniah Trabzuni(King Faisal Specialist Hospital & Research Centre), Juan C. Troncoso(Johns Hopkins University), Marcel van der Brug(National Institutes of Health), Michael E. Weale(Guy's Hospital), Richard M. O’Brien(Johns Hopkins University), Robert Johnson(University of Maryland, Baltimore), Robert Walker(University of Edinburgh), Ronald H. Zielke(University of Maryland, Baltimore), Sampath Arepalli(National Institutes of Health), Mina Ryten(National Hospital for Neurology and Neurosurgery), Andrew Singleton(National Institutes of Health), Y.F. Ramos(Leiden University Medical Center), Harald H.H. Göring(Texas Biomedical Research Institute), Myriam Fornage(The University of Texas Health Science Center at Houston), Ching‐Ti Liu(Wake Forest University), Sina A. Gharib(University of Washington), Barbara E. Stranger(University of Chicago), Philip L. De Jager(Brigham and Women's Hospital), Abraham Aviv(Rutgers, The State University of New Jersey), Daniel Levy(National Heart Lung and Blood Institute), Joanne M. Murabito(Boston University), Peter J. Munson(National Institutes of Health), Tianxiao Huan(National Heart Lung and Blood Institute), Albert Hofman(Erasmus MC), André G. Uitterlinden(Erasmus MC), Fernando Rivadeneira(Erasmus MC), Jeroen van Rooij(Erasmus University Rotterdam), Lisette Stolk(Erasmus University Rotterdam), Linda Broer(Erasmus University Rotterdam), Michaël Verbiest(Erasmus University Rotterdam), Mila Jhamai(Erasmus University Rotterdam), Pascal Arp(Erasmus University Rotterdam), Andres Metspalu(Estonian Biocentre), Liina Tserel(University of Tartu), Lili Milani(Estonian Biocentre), Nilesh J. Samani(University of Leicester), Pärt Peterson(University of Tartu), Silva Kasela(Estonian Biocentre), Veryan Codd(University of Leicester), Annette Peters(Center for Environmental Health), Cavin Ward‐Caviness(Helmholtz Zentrum München), Christian Herder(Deutsches Diabetes-Zentrum e.V.), Mélanie Waldenberger(Center for Environmental Health), Michael Roden(Düsseldorf University Hospital), Paula Singmann(Center for Environmental Health), Sonja Zeilinger(Center for Environmental Health), Thomas Illig(Medizinische Hochschule Hannover), Georg Homuth(Universitätsmedizin Greifswald), Hans J. Grabe(Universitätsmedizin Greifswald), Henry Völzke(Universitätsmedizin Greifswald), Leif Steil(Universitätsmedizin Greifswald), Thomas Kocher(Universitätsmedizin Greifswald), Anna Murray(University of Exeter), David Melzer(University of Exeter), Hanieh Yaghootkar(University of Exeter), Stefania Bandinelli(Azienda Sanitaria di Firenze), Eric K. Moses(The University of Western Australia), 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(Broad Institute), Allan F. McRae(The University of Queensland), Jennifer A. Smith(University of Michigan), Sharon L. R. Kardia(University of Michigan), Iiris Hovatta(University of Helsinki), Markus Perola(Finnish Institute for Health and Welfare), Samuli Ripatti(University of Helsinki), Veikko Salomaa(Finnish Institute for Health and Welfare), Anjali K. Henders(The University of Queensland), Nicholas G. Martin(QIMR Berghofer Medical Research Institute), Alicia K. Smith(Emory University), Divya Mehta(Max Planck Institute of Psychiatry), Elisabeth B. Binder(Max Planck Institute of Psychiatry), K. Maria Nylocks(Emory University), Elizabeth M. Kennedy(Emory University), Torsten Klengel(Max Planck Institute of Psychiatry), Jingzhong Ding(Wake Forest University), Astrid M. Suchy‐Dicey(University of Washington), Daniel A. Enquobahrie(University of Washington), Jennifer A. Brody(University of Washington), Jerome I. Rotter(The Lundquist Institute), Yii‐Der Ida Chen(The Lundquist Institute), Jeanine J. Houwing‐Duistermaat(Leiden University Medical Center), M. 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(Jackson Laboratory), Towfique Raj(Harvard University), Noman Bakhshi(The University of Sydney), Qiao‐Ping Wang(The University of Sydney), Lisa J. Oyston(The University of Sydney), Bruce M. Psaty(Group Health Cooperative), Russell P. Tracy(University of Vermont), 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), Jian Yang(The University of Queensland), Lude Franke(University Medical Center Groningen), Johannes Kettunen(Finnish Institute for Health and Welfare), Peter M. Visscher(The University of Queensland), G. Gregory Neely(The University of Sydney), Ron Korstanje(Jackson Laboratory), Robert L. Hanson(National Institutes of Health), Holger Prokisch(Helmholtz Zentrum München), Luigi Ferrucci(National Institute on Aging), Tõnu Esko(Broad Institute), Alexander Teumer(Universitätsmedizin Greifswald), Joyce B. J. van Meurs(Erasmus University Rotterdam), Andrew D. Johnson(National Heart Lung and Blood Institute)
Cited by 753Open Access
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.
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