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

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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216914/
https://www.ncbi.nlm.nih.gov/pubmed/25249537
http://dx.doi.org/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.
author_facet 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.
author_sort Shah, Sonia
collection PubMed
description 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.
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spelling pubmed-42169142015-05-01 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. Visscher, Peter M. Genome Res Research 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. Cold Spring Harbor Laboratory Press 2014-11 /pmc/articles/PMC4216914/ /pubmed/25249537 http://dx.doi.org/10.1101/gr.176933.114 Text en © 2014 Shah et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
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.
Genetic and environmental exposures constrain epigenetic drift over the human life course
title Genetic and environmental exposures constrain epigenetic drift over the human life course
title_full Genetic and environmental exposures constrain epigenetic drift over the human life course
title_fullStr Genetic and environmental exposures constrain epigenetic drift over the human life course
title_full_unstemmed Genetic and environmental exposures constrain epigenetic drift over the human life course
title_short Genetic and environmental exposures constrain epigenetic drift over the human life course
title_sort genetic and environmental exposures constrain epigenetic drift over the human life course
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216914/
https://www.ncbi.nlm.nih.gov/pubmed/25249537
http://dx.doi.org/10.1101/gr.176933.114
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