Genetic and environmental exposures constrain epigenetic drift over the human life course

Shah, Sonia, McRae, Allan F., Marioni, Riccardo E., Harris, Sarah E., Gibson, Jude, Henders, Anjali K., Redmond, Paul, Cox, Simon R., Pattie, Alison, Corley, Janie, Murphy, Lee, Martin, Nicholas G., Montgomery, Grant W., Starr, John M., Wray, Naomi R., Deary, Ian J. and Visscher, Peter M. (2014) Genetic and environmental exposures constrain epigenetic drift over the human life course. Genome Research, 24 11: 1725-1733. doi:10.1101/gr.176933.114

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Author Shah, Sonia
McRae, Allan F.
Marioni, Riccardo E.
Harris, Sarah E.
Gibson, Jude
Henders, Anjali K.
Redmond, Paul
Cox, Simon R.
Pattie, Alison
Corley, Janie
Murphy, Lee
Martin, Nicholas G.
Montgomery, Grant W.
Starr, John M.
Wray, Naomi R.
Deary, Ian J.
Visscher, Peter M.
Title Genetic and environmental exposures constrain epigenetic drift over the human life course
Journal name Genome Research   Check publisher's open access policy
ISSN 1088-9051
Publication date 2014-11-01
Year available 2014
Sub-type Article (original research)
DOI 10.1101/gr.176933.114
Open Access Status File (Publisher version)
Volume 24
Issue 11
Start page 1725
End page 1733
Total pages 9
Place of publication Cold Spring Harbor, NY, United States
Publisher Cold Spring Harbor Laboratory Press
Language eng
Subject 1311 Genetics
2716 Genetics (clinical)
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.
Keyword Dna Methylation
Genotype Imputation
Hematopoietic Stem
Wide Association
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID MR/K026992/1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 42 times in Thomson Reuters Web of Science Article | Citations
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