Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
26490707
TITLE
The transcriptional landscape of age in human peripheral blood.
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 PUBLISHED
2015
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2015/01/16
accepted 2015/09/07
entrez 2015/10/23 06:00
pubmed 2015/10/23 06:00
medline 2015/10/23 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Peters MJ Peters Marjolein J MJ Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Joehanes R Joehanes Roby R Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20817, USA.
Pilling LC Pilling Luke C LC Epidemiology and Public Health, University of Exeter Medical School, Exeter EX4 1DB, UK.
Schurmann C Schurmann Claudia C 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.
Conneely KN Conneely Karen N KN Department of Human Genetics, School of Medicine, Emory University, Atlanta, Georgia 30301, USA.
Powell J Powell Joseph J The Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4000, Australia.
Reinmaa E Reinmaa Eva E Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.
Sutphin GL Sutphin George L GL Nathan Shock Center of Excellence in the Basic Biology of Aging, The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Zhernakova A Zhernakova Alexandra A Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9700RB, The Netherlands.
Schramm K Schramm Katharina K Institute of Human Genetics, Technical University Munich, Munich 85540, Germany.
Wilson YA Wilson Yana A YA 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.
Kobes S Kobes Sayuko S Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Phoenix, Arizona 85001, USA.
Tukiainen T Tukiainen Taru T Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki 00131, Finland.
NABEC/UKBEC Consortium
Ramos YF Ramos Yolande F YF Department of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
Göring HH Göring Harald H H HH Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.
Fornage M Fornage Myriam M Institute of Molecular Medicine, University of Texas Health Sciences Center at Houston, Houston, Texas 77001, USA.
Liu Y Liu Yongmei Y Department of Epidemiology and Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27101, USA.
Gharib SA Gharib Sina A SA Computational Medicine Core, Center for Lung Biology, University of Washington, Seattle, Washington 98101, USA.
Stranger BE Stranger Barbara E BE Section of Genetic Medicine, Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois 60290, USA.
De Jager PL De Jager Philip L PL Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02108, USA.
Aviv A Aviv Abraham A Center of Human Development and Aging, New Jersey Medical School, Newark 07101, USA.
Levy D Levy Daniel D Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20817, USA.
Murabito JM Murabito Joanne M JM General Internal Medicine Section, Boston University, Boston, Massachusetts 02108, USA.
Munson PJ Munson Peter J PJ The Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20817, USA.
Huan T Huan Tianxiao T Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20817, USA.
Hofman A Hofman Albert A Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000CA, The Netherlands.
Uitterlinden AG Uitterlinden André G AG Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000CA, The Netherlands.
Rivadeneira F Rivadeneira Fernando F Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000CA, The Netherlands.
van Rooij J van Rooij Jeroen J Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Stolk L Stolk Lisette L Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Broer L Broer Linda L Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Verbiest MM Verbiest Michael M P J MM Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Jhamai M Jhamai Mila M Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Arp P Arp Pascal P Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Metspalu A Metspalu Andres A Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.
Tserel L Tserel Liina L Molecular Pathology, Institute of Biomedicine, University of Tartu, Tartu 0794, Estonia.
Milani L Milani Lili L Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.
Samani NJ Samani Nilesh J NJ National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE1, UK.
Peterson P Peterson Pärt P Molecular Pathology, Institute of Biomedicine, University of Tartu, Tartu 0794, Estonia.
Kasela S Kasela Silva S Institute of Molecular and Cell Biology, Estonian Genome Center, University of Tartu, Tartu 0794, Estonia.
Codd V Codd Veryan V National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE1, UK.
Peters A Peters Annette A Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.
Ward-Caviness CK Ward-Caviness Cavin K CK Institute of Epidemiologie II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.
Herder C Herder Christian C Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf 40593, Germany.
Waldenberger M Waldenberger Melanie M Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.
Roden M Roden Michael M Division of Endocrinology and Diabetology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf 40593, Germany.
Singmann P Singmann Paula P Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.
Zeilinger S Zeilinger Sonja S Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg 85764, Germany.
Illig T Illig Thomas T Hannover Unified Biobank, Hannover Medical School, Hannover 30519, Germany.
Homuth G Homuth Georg G Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17493, Germany.
Grabe HJ Grabe Hans-Jörgen HJ Department of Psychiatry and Psychotherapy, Helios Hospital Stralsund, University Medicine Greifswald, Greifswald 17489, Germany.
Völzke H Völzke Henry H Institute for Community Medicine, University Medicine Greifswald, Greifswald 17489, Germany.
Steil L Steil Leif L Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17493, Germany.
Kocher T Kocher Thomas T Unit of Periodontology, Department of Restorative Dentistry, Periodontology and Endodontology, University Medicine Greifswald, Greifswald 17489, Germany.
Murray A Murray Anna A Epidemiology and Public Health, University of Exeter Medical School, Exeter EX4 1DB, UK.
Melzer D Melzer David D Epidemiology and Public Health, University of Exeter Medical School, Exeter EX4 1DB, UK.
Yaghootkar H Yaghootkar Hanieh H Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
Bandinelli S Bandinelli Stefania S Geriatric Unit, Azienda Sanitaria di Firenze, Florence 50123, Italy.
Moses EK Moses Eric K EK 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.
Kent JW Kent Jack W JW Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.
Curran JE Curran Joanne E JE Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.
Johnson MP Johnson Matthew P MP Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.
Williams-Blangero S Williams-Blangero Sarah S Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.
Westra HJ Westra Harm-Jan HJ Partners Center for Personalized Genetic Medicine, Boston, Massachusetts 02108, USA.
McRae AF McRae Allan F AF University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4000, Australia.
Smith JA Smith Jennifer A JA Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48103, USA.
Kardia SL Kardia Sharon L R SL Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48103, USA.
Hovatta I Hovatta Iiris I Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki 00100, Finland.
Perola M Perola Markus M Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki 00131, Finland.
Ripatti S Ripatti Samuli S Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki 00100, Finland.
Salomaa V Salomaa Veikko V Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki 00131, Finland.
Henders AK Henders Anjali K AK The Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4000, Australia.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4000, Australia.
Smith AK Smith Alicia K AK Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30301, USA.
Mehta D Mehta Divya D Max-Planck Institute of Psychiatry, Munich 80331, Germany.
Binder EB Binder Elisabeth B EB Max-Planck Institute of Psychiatry, Munich 80331, Germany.
Nylocks KM Nylocks K Maria KM Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30301, USA.
Kennedy EM Kennedy Elizabeth M EM Department of Human Genetics, School of Medicine, Emory University, Atlanta, Georgia 30301, USA.
Klengel T Klengel Torsten T Max-Planck Institute of Psychiatry, Munich 80331, Germany.
Ding J Ding Jingzhong J Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 27101, USA.
Suchy-Dicey AM Suchy-Dicey Astrid M AM Department of Epidemiology, University of Washington, Seattle, Washington 98101, USA.
Enquobahrie DA Enquobahrie Daniel A DA Department of Epidemiology, University of Washington, Seattle, Washington 98101, USA.
Brody J Brody Jennifer J Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98101, USA.
Rotter JI Rotter Jerome I JI Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90501, USA.
Chen YD Chen Yii-Der I YD Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90501, USA.
Houwing-Duistermaat J Houwing-Duistermaat Jeanine J Department of Medical Statistics, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
Kloppenburg M Kloppenburg Margreet M Department of Clinical Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
Slagboom PE Slagboom P Eline PE Department of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
Helmer Q Helmer Quinta Q Department of Medical Statistics, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
den Hollander W den Hollander Wouter W Department of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
Bean S Bean Shannon S Nathan Shock Center of Excellence in the Basic Biology of Aging, The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Raj T Raj Towfique T Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02138, USA.
Bakhshi N Bakhshi Noman N 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.
Wang QP Wang Qiao Ping QP 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.
Oyston LJ Oyston Lisa J LJ 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.
Psaty BM Psaty Bruce M BM Group Health Research Institute, Group Health Cooperative, Seattle, Washington 98195, USA.
Tracy RP Tracy Russell P RP Department of Pathology, University of Vermont College of Medicine, Colchester, Vermont 98195, USA.
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4000, Australia.
Turner ST Turner Stephen T ST Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota 55901, USA.
Blangero J Blangero John J Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78201, USA.
Meulenbelt I Meulenbelt Ingrid I Department of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands.
Ressler KJ Ressler Kerry J KJ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30301, USA.
Yang J Yang Jian J University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4000, Australia.
Franke L Franke Lude L Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9700RB, The Netherlands.
Kettunen J Kettunen Johannes J Computational Medicine, Institute of Health Sciences, Faculty of Medicine, University of Oulu, Oulu 90570, Finland.
Visscher PM Visscher Peter M PM University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4000, Australia.
Neely GG Neely G Gregory GG 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.
Korstanje R Korstanje Ron R Nathan Shock Center of Excellence in the Basic Biology of Aging, The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Hanson RL Hanson Robert L RL Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Phoenix, Arizona 85001, USA.
Prokisch H Prokisch Holger H Institute of Human Genetics, Technical University Munich, Munich 85540, Germany.
Ferrucci L Ferrucci Luigi L Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 21218, USA.
Esko T Esko Tonu T Department of Genetics, Harvard Medical School, Boston, Massachusetts 02108, USA.
Teumer A Teumer Alexander A Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17493, Germany.
van Meurs JB van Meurs Joyce B J JB Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam 3000CA, The Netherlands.
Johnson AD Johnson Andrew D AD Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20817, USA.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Nalls Michael A MA
Hernandez Dena G DG
Cookson Mark R MR
Gibbs Raphael J RJ
Hardy John J
Ramasamy Adaikalavan A
Zonderman Alan B AB
Dillman Allissa A
Traynor Bryan B
Smith Colin C
Longo Dan L DL
Trabzuni Daniah D
Troncoso Juan J
van der Brug Marcel M
Weale Michael E ME
O'Brien Richard R
Johnson Robert R
Walker Robert R
Zielke Ronald H RH
Arepalli Sampath S
Ryten Mina M
Singleton Andrew B AB
JOURNAL
VOLUME: 6
ISSUE:
TITLE: Nature communications
ISOABBREVIATION: Nat Commun
YEAR: 2015
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2041-1723
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Commun
COUNTRY: England
ISSNLINKING: 2041-1723
NLMUNIQUEID: 101528555
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTID AGENCY COUNTRY
P30 DK063491 NIDDK NIH HHS United States
R01HL105756 NHLBI NIH HHS United States
UL1 TR000124 NCATS NIH HHS United States
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OTHERID SOURCE
PMC4639797 NLM