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
25633388
TITLE
DNA methylation age of blood predicts all-cause mortality in later life.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
DNA methylation levels change with age. Recent studies have identified biomarkers of chronological age based on DNA methylation levels. It is not yet known whether DNA methylation age captures aspects of biological age.
RESULTS NlmCategory: RESULTS
Here we test whether differences between people's chronological ages and estimated ages, DNA methylation age, predict all-cause mortality in later life. The difference between DNA methylation age and chronological age (Δage) was calculated in four longitudinal cohorts of older people. Meta-analysis of proportional hazards models from the four cohorts was used to determine the association between Δage and mortality. A 5-year higher Δage is associated with a 21% higher mortality risk, adjusting for age and sex. After further adjustments for childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease, and APOE e4 status, there is a 16% increased mortality risk for those with a 5-year higher Δage. A pedigree-based heritability analysis of Δage was conducted in a separate cohort. The heritability of Δage was 0.43.
CONCLUSIONS NlmCategory: CONCLUSIONS
DNA methylation-derived measures of accelerated aging are heritable traits that predict mortality independently of health status, lifestyle factors, and known genetic factors.
DATE PUBLISHED
2015
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/07/10
accepted 2015/01/12
aheadofprint 2015/01/30
entrez 2015/01/31 06:00
pubmed 2015/01/31 06:00
medline 2015/12/15 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Marioni RE Marioni Riccardo E RE Queensland Brain Institute, The University of Queensland, Brisbane, 4072, QLD, Australia. riccardo.marioni@ed.ac.uk.
Shah S Shah Sonia S University of Queensland Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, 4072, QLD, Australia. s.shah1@uq.edu.au.
McRae AF McRae Allan F AF University of Queensland Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, 4072, QLD, Australia. a.mcrae@uq.edu.au.
Chen BH Chen Brian H BH Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD, 01702, USA. brian.chen@nih.gov.
Colicino E Colicino Elena E Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA. ecolicin@hsph.harvard.edu.
Harris SE Harris Sarah E SE Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK. Sarah.Harris@igmm.ed.ac.uk.
Gibson J Gibson Jude J Wellcome Trust Clinical Research Facility, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK. jgibson6@staffmail.ed.ac.uk.
Henders AK Henders Anjali K AK Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, 4029, QLD, Australia. Anjali.Henders@qimrberghofer.edu.au.
Redmond P Redmond Paul P Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK. paul.redmond@ed.ac.uk.
Cox SR Cox Simon R SR Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK. simon.cox@ed.ac.uk.
Pattie A Pattie Alison A Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK. Alison.Pattie@ed.ac.uk.
Corley J Corley Janie J Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK. janie.corley@ed.ac.uk.
Murphy L Murphy Lee L Wellcome Trust Clinical Research Facility, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK. Lee.Murphy@ed.ac.uk.
Martin NG Martin Nicholas G NG Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, 4029, QLD, Australia. Nick.Martin@qimrberghofer.edu.au.
Montgomery GW Montgomery Grant W GW Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, 4029, QLD, Australia. Grant.Montgomery@qimrberghofer.edu.au.
Feinberg AP Feinberg Andrew P AP Departments of Medicine, Molecular Biology/Genetics, Oncology, and Biostatistics, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. afeinberg@jhu.edu.
Fallin MD Fallin M Daniele MD Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, 21205, USA. dfallin@jhu.edu.
Multhaup ML Multhaup Michael L ML Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. mmulthaup@gmail.com.
Jaffe AE Jaffe Andrew E AE Lieber Institute for Brain Development, Baltimore, MD, 21205, USA. andrew.jaffe@libd.org.
Joehanes R Joehanes Roby R Hebrew Senior Life, Boston, MA, 02131, USA. robyjoehanes@hsl.harvard.edu.
Schwartz J Schwartz Joel J Department of Epidemiology, Harvard T.H. Chan School of Public Health, 665 Huntington Ave, Boston, MA, 02115, USA. jschwrtz@hsph.harvard.edu.
Just AC Just Allan C AC Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA. acjust@hsph.harvard.edu.
Lunetta KL Lunetta Kathryn L KL Department of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA. klunetta@bu.edu.
Murabito JM Murabito Joanne M JM Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, 02118, USA. murabito@bu.edu.
Starr JM Starr John M JM Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9JZ, UK. jstarr@staffmail.ed.ac.uk.
Horvath S Horvath Steve S Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, CA, 90095, USA. shorvath@mednet.ucla.edu.
Baccarelli AA Baccarelli Andrea A AA Department of Epidemiology, Harvard T.H. Chan School of Public Health, 665 Huntington Ave, Boston, MA, 02115, USA. abaccare@hsph.harvard.edu.
Levy D Levy Daniel D Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD, 01702, USA. levyd@nhlbi.nih.gov.
Visscher PM Visscher Peter M PM University of Queensland Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, 4072, QLD, Australia. peter.visscher@uq.edu.au.
Wray NR Wray Naomi R NR Queensland Brain Institute, The University of Queensland, Brisbane, 4072, QLD, Australia. naomi.wray@uq.edu.au.
Deary IJ Deary Ian J IJ Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK. i.deary@ed.ac.uk.
INVESTIGATORS
JOURNAL
VOLUME: 16
ISSUE:
TITLE: Genome biology
ISOABBREVIATION: Genome Biol.
YEAR: 2015
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1474-760X
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Genome Biol
COUNTRY: England
ISSNLINKING: 1474-7596
NLMUNIQUEID: 100960660
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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GRANTS
GRANTID AGENCY COUNTRY
BB/F019394/1 Biotechnology and Biological Sciences Research Council United Kingdom
CZB/4/505 Chief Scientist Office United Kingdom
ETM/55 Chief Scientist Office United Kingdom
G0700704 Medical Research Council United Kingdom
MR/K026992/1 Medical Research Council United Kingdom
R01 ES020268 NIEHS NIH HHS United States
R01AG029451 NIA NIH HHS United States
R01ES015172 NIEHS NIH HHS United States
R01ES021733 NIEHS NIH HHS United States
Biotechnology and Biological Sciences Research Council United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Aged
Aging genetics
Blood metabolism
Cause of Death metabolism
Cohort Studies metabolism
DNA Methylation genetics
Demography genetics
Female genetics
Humans genetics
Inheritance Patterns genetics
Leukocyte Count genetics
Male genetics
Mortality genetics
Risk Factors genetics
Survival Analysis genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC4350614 NLM