The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Genetic and environmental exposures constrain epigenetic drift over the human life course
Open accessAbstract
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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Cites
Fitting Linear Mixed-Effects Models Using lme4
Bates, D., Mächler, M., Bolker, B., & Walker, S. (2015) · Journal of Statistical Software · doi:10.18637/jss.v067.i01 · Cited by 86,835
A map of human genome variation from population-scale sequencing.
The 1000 Genomes Project Consortium (2010) · Nature · doi:10.1038/nature09534 · Cited by 7,877
DNA methylation age of human tissues and cell types
Horvath, S. (2013) · Genome Biology · doi:10.1186/gb-2013-14-10-r115 · Cited by 7,075
Genome-wide methylation profiles reveal quantitative views of human aging rates
Hannum, G., Guinney, J., Zhao, L., Zhang, L., Hughes, G., Sadda, S., Klotzle, B., Bibikova, M., Fan, J.-B., Gao, Y., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.10.016 · Cited by 4,270
Targeted mutation of the DNA methyltransferase gene results in embryonic lethality
Li, E., Bestor, T. H., & Jaenisch, R. (1992) · Cell · doi:10.1016/0092-8674(92)90611-f · Cited by 3,984
Epigenetic differences arise during the lifetime of monozygotic twins
Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., Heine-Suñer, D., Cigudosa, J. C., Urioste, M., Benitez, J., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500398102 · Cited by 3,602
DNA methylation arrays as surrogate measures of cell mixture distribution
Houseman, E. A., Accomando, W. P., Koestler, D. C., Christensen, B. C., Marsit, C. J., Nelson, H. H., Wiencke, J. K., & Kelsey, K. T. (2012) · BMC Bioinformatics · doi:10.1186/1471-2105-13-86 · Cited by 3,175
Environmental epigenomics and disease susceptibility
Jirtle, R. L., & Skinner, M. K. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2045 · Cited by 2,492
Du, P., Zhang, X., Huang, C.-C., Jafari, N., Kibbe, W. A., Hou, L., & Lin, S. M. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-587 · Cited by 2,136
Fast and accurate genotype imputation in genome-wide association studies through pre-phasing
Howie, B., Fuchsberger, C., Stephens, M., Marchini, J., & Abecasis, G. R. (2012) · Nature Genetics · doi:10.1038/ng.2354 · Cited by 1,737
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Self-citationEpigenetic Signatures of Cigarette Smoking
Joehanes, R., Just, A. C., Marioni, R. E., Pilling, L. C., Reynolds, L. M., Mandaviya, P. R., Guan, W., Xu, T., Elks, C. E., Aslibekyan, S., et al. (2016) · Circulation: Cardiovascular Genetics · doi:10.1161/circgenetics.116.001506 · Cited by 929
Self-citationDNA methylation and healthy human aging
Jones, M. J., Goodman, S. J., & Kobor, M. S. (2015) · Aging Cell · doi:10.1111/acel.12349 · Cited by 928
Systematic identification of genetic influences on methylation across the human life course
Gaunt, T. R., Shihab, H. A., Hemani, G., Min, J. L., Woodward, G., Lyttleton, O., Zheng, J., Duggirala, A., McArdle, W. L., Ho, K., et al. (2016) · Genome Biology · doi:10.1186/s13059-016-0926-z · Cited by 598
Marioni, R. E., Shah, S., McRae, A. F., Ritchie, S. J., Muniz-Terrera, G., Harris, S. E., Gibson, J., Redmond, P., Cox, S. R., Pattie, A., et al. (2015) · International Journal of Epidemiology · doi:10.1093/ije/dyu277 · Cited by 560
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Metadata
- Authors
- Shah, S., McRae, A. F., Marioni, R. E., Harris, S. E., Gibson, J., Henders, A. K., Redmond, P., Cox, S. R., Pattie, A., Corley, J., Murphy, L., Martin, N. G., Montgomery, G. W., Starr, J. M., Wray, N. R., Deary, I. J., & Visscher, P. M.
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2014-09-23
- Volume
- 24
- Issue
- 11
- Pages
- 1725-1733
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- OpenAlex
- W2102093038
- Cited by
- 169
- References
- 18
- Type
- posted content
- Language
- en
- Open access
- bronze
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- Shah, S., McRae, A. F., Marioni, R. E., Harris, S. E., Gibson, J., Henders, A. K., Redmond, P., Cox, S. R., Pattie, A., Corley, J., Murphy, L., Martin, N. G., Montgomery, G. W., Starr, J. M., Wray, N. R., Deary, I. J., & Visscher, P. M. (2014). Genetic and environmental exposures constrain epigenetic drift over the human life course. Genome Research. https://doi.org/10.1101/gr.176933.114
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