Child abuse and epigenetic mechanisms of disease risk
Open accessAbstract
Background Child abuse is highly prevalent and associated with increased risk for a range of health problems including: cancer, cardiovascular disease, diabetes, psychiatric disorders, and other health problems. Little is currently known about the mechanism by which early adversity confers risk for health problems later in life. Purpose To determine if there are epigenetic differences associated with child maltreatment that may help explain association between adverse childhood experiences and later health problems. Methods As part of a study examining genetic and environmental factors associated with depression, saliva DNA specimens were collected on 96 maltreated children removed from their parents due to abuse or neglect and 96 demographically-matched control children between 2003 and 2010. In 2011, the Illumina 450K BeadChip was used on stored DNA specimens and analyzed to examine whole-genome methylation differences between maltreated and control children. Results After controlling for multiple comparisons, maltreated and control children had significantly different methylation values at 2868 CpG sites (p< 5.0 × 10−7, all sites; average methylation difference per site=17%; range 1%–62%). The gene set contained numerous markers of diseases and biological processes related to the health problems associated with early childhood adversity. Conclusions While replication is required, this study suggests that epigenetic mechanisms may be associated with risk for health problems later in life in maltreated children. This study lays the groundwork for future studies examining health and methylation measures to further characterize the role of epigenetic mechanisms in conferring risk for medical problems in individuals with histories of early adversity.
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Presence of ELS/CT is associated with significant differences in methylation in 2,868 CpG sites on genes of all 23 chromosomes.
“Yang et al. (410) reported significant differences in methylation in 2,868 CpG sites on genes of all 23 chromosomes with respect to presence of ELS/CT, while Essex et al. (411) described similar transgenerational results in more than 150 of 28,000 CpG sites in a prospective study assessing parental stress and its consequences in their offspring.”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [410]
The Results (‘Group Differences in Methylation’) report significant differences at 2,868 CpG sites between maltreated and control children, with sites identified on all 23 chromosomes. But the same section places 524 of those sites in intergenic regions, so the claim that all 2,868 sites were on genes is not supported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn that EWAS, comparison to a pathway database of disorder-associated biomarkers showed significant enrichment for epigenetic changes in genes related to a diverse range of neoplasms including lung cancer, colorectal cancer and breast cancer.
“When comparing the results to a pathway database of disorder-associated biomarkers, authors discerned a significant enrichment for epigenetic changes in genes related to a diverse range of neoplasms including lung cancer, colorectal cancer and breast cancer (Yang et al., 2013).”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Yang et al., 2013
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Experimental — accuracy not yet measuredAn EWAS comparing maltreated children (n=96) removed from their parents by protective services with demographically matched children (n=96) found 2,868 significantly differentially methylated saliva CpG sites mainly situated in promoter regions and gene bodies.
“An EWAS comparing maltreated children (n=96) removed from their parents by protective services with demographically matched children (n=96) found 2,868 significantly differentially methylated saliva CpG sites mainly situated in promoter regions and gene bodies.”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Yang et al., 2013
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- Authors
- Yang, B.-Z., Zhang, H., Ge, W., Weder, N., Douglas-Palumberi, H., Perepletchikova, F., Gelernter, J., & Kaufman, J.
- Affiliations
- Yale University (US)
- Child Mind Institute (US)
- Corresponding author
- Kaufman, Joan
- Venue
- American Journal of Preventive Medicine
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 44
- Issue
- 2
- Pages
- 101-107
- ISSN
- 0749-3797 (ISSN-L)
- PMC
- PMC3758252
- OpenAlex
- W1990674768
- Semantic Scholar
- a6bf3731a92108782314ed85b6ee5a917d1c83f9
- Cited by
- 256
- References
- 73
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 10 · 2023: 19 · 2022: 36 · 2021: 20 · 2020: 20 · 2019: 17 · 2018: 23 · 2017: 14 · 2016: 22 · 2015: 33 · 2014: 24 · 2013: 6
- FWCI
- 31.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Preventive Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (K01 DA24758, K99/R00 DA022891, T32 MH067763, DA12849, DA12690, AA017535, AA11330R01, MH077087)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Safety Research › Child Welfare and Adoption
- Keywords
- child abuse, epigenetics, DNA methylation, childhood adversity, depression, CpG sites, health risks, neglect, salivary DNA, gene-environment interaction
- MeSH terms
- Adolescent, Child, Child Abuse, Child, Preschool, DNA, Female, Humans, Male, Risk Factors, Saliva, Case-Control Studies, DNA Methylation, Oligonucleotide Array Sequence Analysis, Epigenesis, Genetic, Genome-Wide Association Study
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