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
25249537
TITLE
Genetic and environmental exposures constrain epigenetic drift over the human life course.
ABSTRACT
Epigenetic mechanisms such as DNA methylation (DNAm) are essential for regulation of gene expression. DNAm is dynamic, influenced by both environmental and genetic factors. Epigenetic drift is the divergence of the epigenome as a function of age due to stochastic changes in methylation. Here we show that epigenetic drift may be constrained at many CpGs across the human genome by DNA sequence variation and by lifetime environmental exposures. We estimate repeatability of DNAm at 234,811 autosomal CpGs in whole blood using longitudinal data (2-3 repeated measurements) on 478 older people from two Scottish birth cohorts--the Lothian Birth Cohorts of 1921 and 1936. Median age was 79 yr and 70 yr, and the follow-up period was ∼10 yr and ∼6 yr, respectively. We compare this to methylation heritability estimated in the Brisbane Systems Genomics Study, a cross-sectional study of 117 families (offspring median age 13 yr; parent median age 46 yr). CpG repeatability in older people was highly correlated (0.68) with heritability estimated in younger people. Highly heritable sites had strong underlying cis-genetic effects. Thirty-seven and 1687 autosomal CpGs were associated with smoking and sex, respectively. Both sets were strongly enriched for high repeatability. Sex-associated CpGs were also strongly enriched for high heritability. Our results show that a large number of CpGs across the genome, as a result of environmental and/or genetic constraints, have stable DNAm variation over the human lifetime. Moreover, at a number of CpGs, most variation in the population is due to genetic factors, despite some sites being highly modifiable by the environment.
2014 Shah et al.; Published by Cold Spring Harbor Laboratory Press.
DATE PUBLISHED
2014 Nov
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2014/09/23
entrez 2014/09/25 06:00
pubmed 2014/09/25 06:00
medline 2015/07/21 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Shah S Shah Sonia S Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Queensland, Australia;
McRae AF McRae Allan F AF Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Queensland, Australia;
Marioni RE Marioni Riccardo E RE Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Queensland, Australia; Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom;
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, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom;
Gibson J Gibson Jude J Wellcome Trust Clinical Research Facility, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, United Kingdom;
Henders AK Henders Anjali K AK QIMR Berghofer Medical Research Institute, Brisbane, 4029, Queensland, Australia;
Redmond P Redmond Paul P Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom;
Cox SR Cox Simon R SR Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom;
Pattie A Pattie Alison A Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom;
Corley J Corley Janie J Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom;
Murphy L Murphy Lee L Wellcome Trust Clinical Research Facility, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, United Kingdom;
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, 4029, Queensland, Australia;
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, Brisbane, 4029, Queensland, Australia;
Starr JM Starr John M JM Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom;
Wray NR Wray Naomi R NR Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Queensland, Australia;
Deary IJ Deary Ian J IJ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom;
Visscher PM Visscher Peter M PM Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Queensland, Australia; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom; University of Queensland Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, 4072, Queensland, Australia peter.visscher@uq.edu.au.
INVESTIGATORS
JOURNAL
VOLUME: 24
ISSUE: 11
TITLE: Genome research
ISOABBREVIATION: Genome Res.
YEAR: 2014
MONTH: Nov
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1549-5469
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Genome Res
COUNTRY: United States
ISSNLINKING: 1088-9051
NLMUNIQUEID: 9518021
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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
MR/K026992/1 Medical Research Council United Kingdom
Biotechnology and Biological Sciences Research Council United Kingdom
Chief Scientist Office United Kingdom
Medical Research Council United Kingdom
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Aged
Aged, 80 and over
Algorithms
Child
Cohort Studies
CpG Islands genetics
Cross-Sectional Studies genetics
DNA Methylation genetics
Family Health genetics
Female genetics
Gene-Environment Interaction genetics
Genetics, Population methods
Genome, Human genetics
Humans genetics
Inheritance Patterns genetics
Male genetics
Middle Aged genetics
Models, Genetic genetics
Polymorphism, Single Nucleotide genetics
Sex Factors genetics
Smoking genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC4216914 NLM