Childhood abuse is associated with methylation of multiple loci in adult DNA
Open accessAbstract
Background: Childhood abuse is associated with increased adult disease risk, suggesting that processes acting over the long-term, such as epigenetic regulation of gene activity, may be involved. DNA methylation is a critical mechanism in epigenetic regulation. We aimed to establish whether childhood abuse was associated with adult DNA methylation profiles. Methods: In 40 males from the 1958 British Birth Cohort we compared genome-wide promoter DNA methylation in blood taken at 45y for those with, versus those without, childhood abuse (n = 12 vs 28). We analysed the promoter methylation of over 20,000 genes and 489 microRNAs, using MeDIP (methylated DNA immunoprecipitation) in triplicate. Results: We found 997 differentially methylated gene promoters (311 hypermethylated and 686 hypomethylated) in association with childhood abuse and these promoters were enriched for genes involved in key cell signaling pathways related to transcriptional regulation and development. Using bisulfite-pyrosequencing, abuse-associated methylation (MeDIP) at the metalloproteinase gene,PM20D1, was validated and then replicated in an additional 27 males. Abuse-associated methylation was observed in 39 microRNAs; in 6 of these, the hypermethylated state was consistent with the hypomethylation of their downstream gene targets. Although distributed across the genome, the differentially methylated promoters associated with child abuse clustered in genome regions of at least one megabase. The observations for child abuse showed little overlap with methylation patterns associated with socioeconomic position. Conclusions: Our observed genome-wide methylation profiles in adult DNA associated with childhood abuse justify the further exploration of epigenetic regulation as a mediating mechanism for long-term health outcomes.
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Adults subjected to childhood abuse had differential methylation in 997 genes, many of which were involved in developmental cell signaling pathways.
“For example, it was shown that adults subjected to childhood abuse had differential methylation in 997 genes, many of which were involved in developmental cell signaling pathways [49].”
Other studies have observed associations between childhood maltreatment and differences in DNA methylation in brain, blood, and gametes.
“Other studies have also observed associations between childhood maltreatment and differences in DNAm in the brain, 58 blood, 59 , 60 and even gametes. 61”
From Epigenetics and depression (2019) · cites this paper as [59]
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Self-citation
- Authors
- Suderman, M., Borghol, N., Pappas, J. J., Pinto Pereira, S. M., Pembrey, M., Hertzman, C., Power, C., & Szyf, M.
- Affiliations
- McGill University (CA)
- University College London (GB)
- University of British Columbia (CA)
- Venue
- BMC Medical Genomics
- Published
- 2014-03-11
- Volume
- 7
- Issue
- 1
- Pages
- 13-13
- ISSN
- 1755-8794 (ISSN-L)
- PMC
- PMC4007631
- OpenAlex
- W1987261032
- Cited by
- 193
- References
- 68
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 9 · 2023: 8 · 2022: 12 · 2021: 22 · 2020: 18 · 2019: 23 · 2018: 16 · 2017: 24 · 2016: 20 · 2015: 21 · 2014: 9
- FWCI
- 10.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Medical Genomics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- McGill University
- Wellcome Trust
- University College London
- University of Bristol
- Canadian Institutes of Health Research (MOP42411)
- Medical Research Council (G0400546, G0000934)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- childhood abuse, DNA methylation, epigenetic regulation, promoter methylation, differentially methylated genes, microRNA methylation, PM20D1, 1958 British birth cohort, adult health outcomes, socioeconomic position, gene expression regulation
- MeSH terms
- Adult, Child, Child Abuse, Humans, Male, Promoter Regions, Genetic, Socioeconomic Factors, Reproducibility of Results, Genome, Human, Cluster Analysis, CpG Islands, DNA Methylation, Base Pairing, MicroRNAs, Genetic Loci, Genetic Association Studies, Wnt Signaling Pathway
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