The transcriptional landscape of age in human peripheral blood.
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.
Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Marjolein J
MJ
Peters
The National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702, USA.|Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20817, USA.
Roby
R
Joehanes
Epidemiology and Public Health, University of Exeter Medical School, Exeter EX4 1DB, UK.
Luke C
LC
Pilling
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17493, Germany.|The Charles Bronfman Institute for Personalized Medicine, Genetics of Obesity &Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York 10029, USA.
Claudia
C
Schurmann
Department of Human Genetics, School of Medicine, Emory University, Atlanta, Georgia 30301, USA.
Karen N
KN
Conneely
Centre for Neurogenetics and Statistical Genomics, Queensland Brain Institute, University of Queensland, St Lucia, Brisbane, Queensland 4000, Australia.|The Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4000, Australia.
Joseph
J
Powell
Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.
Eva
E
Reinmaa
Nathan Shock Center of Excellence in the Basic Biology of Aging, The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
George L
GL
Sutphin
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9700RB, The Netherlands.
Alexandra
A
Zhernakova
Institute of Human Genetics, Helmholz Zentrum München - German Research Center for Environmental Health, Neuherberg 85764, Germany.|Institute of Human Genetics, Technical University Munich, Munich 85540, Germany.
Katharina
K
Schramm
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.
Yana A
YA
Wilson
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Phoenix, Arizona 85001, USA.
Sayuko
S
Kobes
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.
Taru
T
Tukiainen
Department of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
Yolande F
YF
Ramos
Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.
Harald H H
HH
Göring
Division of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Sciences, Center at Houston, Texas 77001, USA.|Institute of Molecular Medicine, University of Texas Health Sciences Center at Houston, Houston, Texas 77001, USA.
Myriam
M
Fornage
Department of Epidemiology and Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27101, USA.
Yongmei
Y
Liu
Computational Medicine Core, Center for Lung Biology, University of Washington, Seattle, Washington 98101, USA.
Sina A
SA
Gharib
Section of Genetic Medicine, Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois 60290, USA.
Barbara E
BE
Stranger
Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02108, USA.
Philip L
PL
De Jager
Center of Human Development and Aging, New Jersey Medical School, Newark 07101, USA.
Abraham
A
Aviv
The National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702, USA.|Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20817, USA.
Daniel
D
Levy
The National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702, USA.|General Internal Medicine Section, Boston University, Boston, Massachusetts 02108, USA.
Joanne M
JM
Murabito
The Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20817, USA.
Peter J
PJ
Munson
The National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702, USA.|Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20817, USA.
Tianxiao
T
Huan
Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000CA, The Netherlands.
Albert
A
Hofman
Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.|Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000CA, The Netherlands.
André G
AG
Uitterlinden
Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.|Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000CA, The Netherlands.
Fernando
F
Rivadeneira
Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Jeroen
J
van Rooij
Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Lisette
L
Stolk
Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Linda
L
Broer
Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Michael M P J
MM
Verbiest
Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Mila
M
Jhamai
Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Pascal
P
Arp
Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.
Andres
A
Metspalu
Molecular Pathology, Institute of Biomedicine, University of Tartu, Tartu 0794, Estonia.
Liina
L
Tserel
Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.
Lili
L
Milani
Department of Cardiovascular Sciences, University of Leicester, Leicester LE1, UK.|National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE1, UK.
Nilesh J
NJ
Samani
Molecular Pathology, Institute of Biomedicine, University of Tartu, Tartu 0794, Estonia.
Pärt
P
Peterson
Institute of Molecular and Cell Biology, Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.
Silva
S
Kasela
Department of Cardiovascular Sciences, University of Leicester, Leicester LE1, UK.|National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE1, UK.
Veryan
V
Codd
Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.
Annette
A
Peters
Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.
Cavin K
CK
Ward-Caviness
Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf 40593, Germany.
Christian
C
Herder
Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.
Melanie
M
Waldenberger
Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf 40593, Germany.|Division of Endocrinology and Diabetology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf 40593, Germany.
Michael
M
Roden
Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.
Paula
P
Singmann
Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.
Sonja
S
Zeilinger
Hannover Unified Biobank, Hannover Medical School, Hannover 30519, Germany.
Thomas
T
Illig
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17493, Germany.
Georg
G
Homuth
Department of Psychiatry and Psychotherapy, Helios Hospital Stralsund, University Medicine Greifswald, Greifswald 17489, Germany.
Hans-Jörgen
HJ
Grabe
Institute for Community Medicine, University Medicine Greifswald, Greifswald 17489, Germany.
Henry
H
Völzke
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17493, Germany.
Leif
L
Steil
Unit of Periodontology, Department of Restorative Dentistry, Periodontology and Endodontology, University Medicine Greifswald, Greifswald 17489, Germany.
Thomas
T
Kocher
Epidemiology and Public Health, University of Exeter Medical School, Exeter EX4 1DB, UK.
Anna
A
Murray
Epidemiology and Public Health, University of Exeter Medical School, Exeter EX4 1DB, UK.
David
D
Melzer
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
Hanieh
H
Yaghootkar
Geriatric Unit, Azienda Sanitaria di Firenze, Florence 50123, Italy.
Stefania
S
Bandinelli
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.
Eric K
EK
Moses
Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.
Jack W
JW
Kent
Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.
Joanne E
JE
Curran
Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.
Matthew P
MP
Johnson
Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.
Sarah
S
Williams-Blangero
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9700RB, The Netherlands.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge 02138, USA.|Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02108, USA.|Partners Center for Personalized Genetic Medicine, Boston, Massachusetts 02108, USA.
Harm-Jan
HJ
Westra
The Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4000, Australia.|University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4000, Australia.
Allan F
AF
McRae
Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48103, USA.
Jennifer A
JA
Smith
Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48103, USA.
Sharon L R
SL
Kardia
Department of Biosciences, University of Helsinki, Helsinki 00100, Finland.|Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki 00100, Finland.
Iiris
I
Hovatta
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.
Markus
M
Perola
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.|Wellcome Trust Sanger Institute, Hinxton, Cambridge CB4, UK.|Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki 00100, Finland.
Samuli
S
Ripatti
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki 00131, Finland.
Veikko
V
Salomaa
The Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4000, Australia.
Anjali K
AK
Henders
QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4000, Australia.
Nicholas G
NG
Martin
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30301, USA.
Alicia K
AK
Smith
Max-Planck Institute of Psychiatry, Munich 80331, Germany.
Divya
D
Mehta
Max-Planck Institute of Psychiatry, Munich 80331, Germany.
Elisabeth B
EB
Binder
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30301, USA.
K Maria
KM
Nylocks
Department of Human Genetics, School of Medicine, Emory University, Atlanta, Georgia 30301, USA.
Elizabeth M
EM
Kennedy
Max-Planck Institute of Psychiatry, Munich 80331, Germany.
Torsten
T
Klengel
Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 27101, USA.
Jingzhong
J
Ding
Department of Epidemiology, University of Washington, Seattle, Washington 98101, USA.
Astrid M
AM
Suchy-Dicey
Department of Epidemiology, University of Washington, Seattle, Washington 98101, USA.
Daniel A
DA
Enquobahrie
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98101, USA.
Jennifer
J
Brody
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90501, USA.
Jerome I
JI
Rotter
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90501, USA.
Yii-Der I
YD
Chen
Department of Medical Statistics, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
Jeanine
J
Houwing-Duistermaat
Department of Rheumatology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.|Department of Clinical Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
Margreet
M
Kloppenburg
Department of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
P Eline
PE
Slagboom
Department of Medical Statistics, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
Quinta
Q
Helmer
Department of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
Wouter
W
den Hollander
Nathan Shock Center of Excellence in the Basic Biology of Aging, The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Shannon
S
Bean
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02138, USA.
Towfique
T
Raj
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.
Noman
N
Bakhshi
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.
Qiao Ping
QP
Wang
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.
Lisa J
LJ
Oyston
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98195, USA.|Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, Washington 98195, USA.|Cardiovascular Health Research Unit, Department of Health Services, University of Washington, Seattle, Washington 98195, USA.|Group Health Research Institute, Group Health Cooperative, Seattle, Washington 98195, USA.
Bruce M
BM
Psaty
Department of Pathology, University of Vermont College of Medicine, Colchester, Vermont 98195, USA.
Russell P
RP
Tracy
QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4000, Australia.
Grant W
GW
Montgomery
Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota 55901, USA.
Stephen T
ST
Turner
Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.
John
J
Blangero
Department of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
Ingrid
I
Meulenbelt
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30301, USA.
Kerry J
KJ
Ressler
The Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4000, Australia.|University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4000, Australia.
Jian
J
Yang
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9700RB, The Netherlands.
Lude
L
Franke
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.|Computational Medicine, Institute of Health Sciences, Faculty of Medicine, University of Oulu, Oulu 90570, Finland.
Johannes
J
Kettunen
The Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4000, Australia.|University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4000, Australia.
Peter M
PM
Visscher
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.
G Gregory
GG
Neely
Nathan Shock Center of Excellence in the Basic Biology of Aging, The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Ron
R
Korstanje
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Phoenix, Arizona 85001, USA.
Robert L
RL
Hanson
Institute of Human Genetics, Helmholz Zentrum München - German Research Center for Environmental Health, Neuherberg 85764, Germany.|Institute of Human Genetics, Technical University Munich, Munich 85540, Germany.
Holger
H
Prokisch
Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 21218, USA.
Luigi
L
Ferrucci
Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge 02138, USA.|Division of Endocrinology, Children's Hospital Boston, Boston, Massachusetts 02108, USA.|Department of Genetics, Harvard Medical School, Boston, Massachusetts 02108, USA.
Tonu
T
Esko
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17493, Germany.
Alexander
A
Teumer
Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Joyce B J
JB
van Meurs
The National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702, USA.|Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20817, USA.
Andrew D
AD
Johnson
D000375:Aging / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D019175:DNA Methylation; D020869:Gene Expression Profiling; D006801:Humans; D059467:Transcriptome; D044465:White People
D015415:Biomarkers