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Am J Psychiatry. 2018 Jun 1;175(6):517-529. doi: 10.1176/appi.ajp.2017.17060693. Epub 2018 Jan 12.

Analysis of DNA Methylation in Young People: Limited Evidence for an Association Between Victimization Stress and Epigenetic Variation in Blood.

Author information

1
From the Social, Genetic, and Developmental Psychiatry Research Centre, the Department of Child and Adolescent Psychiatry, and the Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King's College London; the National and Specialist Clinic for Child Traumatic Stress and Anxiety Disorders, South London and Maudsley NHS Foundation Trust, London; the Department of Psychology and Neuroscience, Social Science Research Institute, and the Center for Genomic and Computational Biology, Duke University, Durham, N.C.; the Department of Psychiatry and Behavioral Sciences, the Department of Population Health Sciences, and the Department of Medicine, Duke University School of Medicine, Durham, N.C.; the Dunedin Multidisciplinary Health and Development Research Unit, University of Otago, Dunedin, New Zealand; and the Complex Disease Epigenetics Group, University of Exeter Medical School, Exeter, U.K.

Abstract

OBJECTIVE:

DNA methylation has been proposed as an epigenetic mechanism by which early-life experiences become "embedded" in the genome and alter transcriptional processes to compromise health. The authors sought to investigate whether early-life victimization stress is associated with genome-wide DNA methylation.

METHOD:

The authors tested the hypothesis that victimization is associated with DNA methylation in the Environmental Risk (E-Risk) Longitudinal Study, a nationally representative 1994-1995 birth cohort of 2,232 twins born in England and Wales and assessed at ages 5, 7, 10, 12, and 18 years. Multiple forms of victimization were ascertained in childhood and adolescence (including physical, sexual, and emotional abuse; neglect; exposure to intimate-partner violence; bullying; cyber-victimization; and crime).

RESULTS:

Epigenome-wide analyses of polyvictimization across childhood and adolescence revealed few significant associations with DNA methylation in peripheral blood at age 18, but these analyses were confounded by tobacco smoking and/or did not survive co-twin control tests. Secondary analyses of specific forms of victimization revealed sparse associations with DNA methylation that did not replicate across different operationalizations of the same putative victimization experience. Hypothesis-driven analyses of six candidate genes in the stress response (NR3C1, FKBP5, BDNF, AVP, CRHR1, SLC6A4) did not reveal predicted associations with DNA methylation in probes annotated to these genes.

CONCLUSIONS:

Findings from this epidemiological analysis of the epigenetic effects of early-life stress do not support the hypothesis of robust changes in DNA methylation in victimized young people. We need to come to terms with the possibility that epigenetic epidemiology is not yet well matched to experimental, nonhuman models in uncovering the biological embedding of stress.

KEYWORDS:

DNA Methylation; Epigenetics; Maltreatment; Stress

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