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Nat Commun. 2015 Oct 22;6:8570. doi: 10.1038/ncomms9570.

The transcriptional landscape of age in human peripheral blood.

Peters MJ1, Joehanes R2,3, Pilling LC4, Schurmann C5,6, Conneely KN7, Powell J8,9, Reinmaa E10, Sutphin GL11, Zhernakova A12, Schramm K13,14, Wilson YA15, Kobes S16, Tukiainen T17,18; NABEC/UKBEC Consortium, Ramos YF19, Göring HH20, Fornage M21,22, Liu Y23, Gharib SA24, Stranger BE25, De Jager PL26, Aviv A27, Levy D2,3, Murabito JM2,28, Munson PJ29, Huan T2,3, Hofman A30, Uitterlinden AG1,30, Rivadeneira F1,30, van Rooij J1, Stolk L1, Broer L1, Verbiest MM1, Jhamai M1, Arp P1, Metspalu A10, Tserel L31, Milani L10, Samani NJ32,33, Peterson P31, Kasela S34, Codd V32,33, Peters A35,36, Ward-Caviness CK35, Herder C37, Waldenberger M35,36, Roden M37,38, Singmann P35,36, Zeilinger S35,36, Illig T39, Homuth G5, Grabe HJ40, Völzke H41, Steil L5, Kocher T42, Murray A4, Melzer D4, Yaghootkar H43, Bandinelli S44, Moses EK45, Kent JW20, Curran JE20, Johnson MP20, Williams-Blangero S20, Westra HJ12,46,47,48, McRae AF49,50, Smith JA51, Kardia SL51, Hovatta I52,53, Perola M10,17,18, Ripatti S17,18,54,55, Salomaa V18, Henders AK9, Martin NG56, Smith AK57, Mehta D58, Binder EB58, Nylocks KM57, Kennedy EM7, Klengel T58, Ding J59, Suchy-Dicey AM60, Enquobahrie DA60, Brody J61, Rotter JI62, Chen YD62, Houwing-Duistermaat J63, Kloppenburg M64,65, Slagboom PE19, Helmer Q63, den Hollander W19, Bean S11, Raj T66, Bakhshi N15, Wang QP15, Oyston LJ15, Psaty BM67,68,69,70, Tracy RP71, Montgomery GW56, Turner ST72, Blangero J20, Meulenbelt I19, Ressler KJ57, Yang J49,50, Franke L12, Kettunen J17,18,73, Visscher PM49,50, Neely GG15, Korstanje R11, Hanson RL16, Prokisch H13,14, Ferrucci L74, Esko T10,46,75,76, Teumer A5, van Meurs JB1, Johnson AD2,3.

Author information

1
Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
2
The National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702, USA.
3
Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20817, USA.
4
Epidemiology and Public Health, University of Exeter Medical School, Exeter EX4 1DB, UK.
5
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17493, Germany.
6
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.
7
Department of Human Genetics, School of Medicine, Emory University, Atlanta, Georgia 30301, USA.
8
Centre for Neurogenetics and Statistical Genomics, Queensland Brain Institute, University of Queensland, St Lucia, Brisbane, Queensland 4000, Australia.
9
The Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4000, Australia.
10
Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.
11
Nathan Shock Center of Excellence in the Basic Biology of Aging, The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
12
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9700RB, The Netherlands.
13
Institute of Human Genetics, Helmholz Zentrum München - German Research Center for Environmental Health, Neuherberg 85764, Germany.
14
Institute of Human Genetics, Technical University Munich, Munich 85540, Germany.
15
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.
16
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Phoenix, Arizona 85001, USA.
17
Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki 00131, Finland.
18
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki 00131, Finland.
19
Department of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
20
Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.
21
Division of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Sciences, Center at Houston, Texas 77001, USA.
22
Institute of Molecular Medicine, University of Texas Health Sciences Center at Houston, Houston, Texas 77001, USA.
23
Department of Epidemiology and Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27101, USA.
24
Computational Medicine Core, Center for Lung Biology, University of Washington, Seattle, Washington 98101, USA.
25
Section of Genetic Medicine, Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois 60290, USA.
26
Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02108, USA.
27
Center of Human Development and Aging, New Jersey Medical School, Newark 07101, USA.
28
General Internal Medicine Section, Boston University, Boston, Massachusetts 02108, USA.
29
The Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20817, USA.
30
Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000CA, The Netherlands.
31
Molecular Pathology, Institute of Biomedicine, University of Tartu, Tartu 0794, Estonia.
32
Department of Cardiovascular Sciences, University of Leicester, Leicester LE1, UK.
33
National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE1, UK.
34
Institute of Molecular and Cell Biology, Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.
35
Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.
36
Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.
37
Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf 40593, Germany.
38
Division of Endocrinology and Diabetology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf 40593, Germany.
39
Hannover Unified Biobank, Hannover Medical School, Hannover 30519, Germany.
40
Department of Psychiatry and Psychotherapy, Helios Hospital Stralsund, University Medicine Greifswald, Greifswald 17489, Germany.
41
Institute for Community Medicine, University Medicine Greifswald, Greifswald 17489, Germany.
42
Unit of Periodontology, Department of Restorative Dentistry, Periodontology and Endodontology, University Medicine Greifswald, Greifswald 17489, Germany.
43
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
44
Geriatric Unit, Azienda Sanitaria di Firenze, Florence 50123, Italy.
45
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.
46
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge 02138, USA.
47
Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02108, USA.
48
Partners Center for Personalized Genetic Medicine, Boston, Massachusetts 02108, USA.
49
The Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4000, Australia.
50
University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4000, Australia.
51
Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48103, USA.
52
Department of Biosciences, University of Helsinki, Helsinki 00100, Finland.
53
Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki 00100, Finland.
54
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB4, UK.
55
Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki 00100, Finland.
56
QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4000, Australia.
57
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30301, USA.
58
Max-Planck Institute of Psychiatry, Munich 80331, Germany.
59
Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 27101, USA.
60
Department of Epidemiology, University of Washington, Seattle, Washington 98101, USA.
61
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98101, USA.
62
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90501, USA.
63
Department of Medical Statistics, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
64
Department of Rheumatology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
65
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
66
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02138, USA.
67
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
68
Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, Washington 98195, USA.
69
Cardiovascular Health Research Unit, Department of Health Services, University of Washington, Seattle, Washington 98195, USA.
70
Group Health Research Institute, Group Health Cooperative, Seattle, Washington 98195, USA.
71
Department of Pathology, University of Vermont College of Medicine, Colchester, Vermont 98195, USA.
72
Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota 55901, USA.
73
Computational Medicine, Institute of Health Sciences, Faculty of Medicine, University of Oulu, Oulu 90570, Finland.
74
Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 21218, USA.
75
Division of Endocrinology, Children's Hospital Boston, Boston, Massachusetts 02108, USA.
76
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02108, 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.

PMID:
26490707
PMCID:
PMC4639797
DOI:
10.1038/ncomms9570
[Indexed for MEDLINE]
Free PMC Article

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