Factors underlying variable DNA methylation in a human community cohort
Open accessAbstract
Epigenetics is emerging as an attractive mechanism to explain the persistent genomic embedding of early-life experiences. Tightly linked to chromatin, which packages DNA into chromosomes, epigenetic marks primarily serve to regulate the activity of genes. DNA methylation is the most accessible and characterized component of the many chromatin marks that constitute the epigenome, making it an ideal target for epigenetic studies in human populations. Here, using peripheral blood mononuclear cells collected from a community-based cohort stratified for early-life socioeconomic status, we measured DNA methylation in the promoter regions of more than 14,000 human genes. Using this approach, we broadly assessed and characterized epigenetic variation, identified some of the factors that sculpt the epigenome, and determined its functional relation to gene expression. We found that the leukocyte composition of peripheral blood covaried with patterns of DNA methylation at many sites, as did demographic factors, such as sex, age, and ethnicity. Furthermore, psychosocial factors, such as perceived stress, and cortisol output were associated with DNA methylation, as was early-life socioeconomic status. Interestingly, we determined that DNA methylation was strongly correlated to the ex vivo inflammatory response of peripheral blood mononuclear cells to stimulation with microbial products that engage Toll-like receptors. In contrast, our work found limited effects of DNA methylation marks on the expression of associated genes across individuals, suggesting a more complex relationship than anticipated.
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Those epigenetic profiles are only weakly correlated with differences in immune cell gene expression.
“However, those epigenetic profiles are only weakly correlated with differences in immune cell gene expression [7], [41], and much remains to be learned about what role epigenetic dynamics play in social genomic effects such as the CTRA.”
From Human Social Genomics (2014) · cites this paper as [41]
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- Authors
- Lam, L. L., Emberly, E., Fraser, H. B., Neumann, S. M., Chen, E., Miller, G. E., & Kobor, M. S.
- Affiliations
- University of British Columbia (CA)
- Simon Fraser University (CA)
- Stanford University (US)
- Child and Family Research Institute (CA)
- Departments of dPsychology and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-10-08
- Volume
- 109
- Issue
- supplement_2
- Pages
- 17253-17260
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3477380
- OpenAlex
- W1970003449
- Cited by
- 476
- References
- 52
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 18 · 2023: 23 · 2022: 30 · 2021: 37 · 2020: 32 · 2019: 31 · 2018: 38 · 2017: 54 · 2016: 42 · 2015: 62 · 2014: 47 · 2013: 29 · 2012: 2
- FWCI
- 17.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institute for Advanced Research
- National Institute of Mental Health (R24MH081797)
- National Institute of Child Health and Human Development (HD058502)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD058502, R01HD058502)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- DNA methylation, epigenetics, childhood socioeconomic status, promoter methylation, peripheral blood mononuclear cells, leukocyte composition, perceived stress, cortisol, Toll-like receptor response, inflammation, gene expression, sex differences, ethnicity, age effects, community-based cohort
- MeSH terms
- Adult, Female, Genetics, Population, Humans, Leukocytes, Life Change Events, Male, Middle Aged, Poverty, Promoter Regions, Genetic, Social Class, Stress, Psychological, Cohort Studies, Gene Expression, DNA Methylation, Principal Component Analysis, Epigenesis, Genetic, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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