Methylation of exons 1D, 1F, and 1Hof the glucocorticoid receptor gene promoter and exposure to adversity in preschool-aged children
Open accessAbstract
Epigenetic modifications to the genome are a key mechanism involved in the biological encoding of experience. Animal studies and a growing body of literature in humans have shown that early adversity is linked to methylation of the gene for the glucocorticoid receptor (GR), which is a key regulator of the hypothalamic–pituitary–adrenal axis as well as a broad range of physiological systems including metabolic and immune function. One hundred eighty-four families participated, including n= 74 with child welfare documentation of moderate-severe maltreatment in the past 6 months. Children ranged in age from 3 to 5 years, and were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors, and a composite variable assessed the number exposures to these adversities. Methylation of regions 1 D, 1 F, and 1 H of the GR gene was measured via sodium bisulfite pyrosequencing. The composite measure of adversity was positively correlated with methylation at exons 1 D and 1 F in the promoter of the GR gene. Individual stress measures were significantly associated with a several CpG sites in these regions. GR gene methylation may be a mechanism of the biobehavioral effects of adverse exposures in young children.
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- Authors
- Tyrka, A. R., Parade, S. H., Eslinger, N. M., Marsit, C. J., Lesseur, C., Armstrong, D. A., Philip, N. S., Josefson, B., & Seifer, R.
- Affiliations
- Brown University (US)
- Butler Hospital (US)
- Dartmouth College (US)
- Bradley Hospital (US)
- Corresponding author
- Tyrka, Audrey R.
- ORCID
- Venue
- Development and Psychopathology
- Publisher
- Cambridge University Press (CUP)
- Published
- 2015-05
- Volume
- 27
- Issue
- 2
- Pages
- 577-585
- ISSN
- 0954-5794 (ISSN-L)
- 1469-2198
- PMC
- PMC5014375
- OpenAlex
- W1755529343
- Cited by
- 60
- References
- 59
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 7 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 8 · 2016: 7 · 2015: 2
- FWCI
- 9.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Development and Psychopathology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (IK2 CX000724)
- National Institute of Mental Health (R01MH083704)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- glucocorticoid receptor gene, DNA methylation, childhood adversity, child abuse, preschool children, epigenetics, hypothalamic-pituitary-adrenal axis, CpG sites, life events, child welfare
- MeSH terms
- Child Abuse, Child, Preschool, Exons, Female, Humans, Hypothalamo-Hypophyseal System, Male, Pituitary-Adrenal System, Promoter Regions, Genetic, Receptors, Glucocorticoid, DNA Methylation, Epigenesis, Genetic
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