Analysis of DNA Methylation in Young People: Limited Evidence for an Association Between Victimization Stress and Epigenetic Variation in Blood
American Journal of Psychiatry
American Psychiatric Publishing
Copyright © 2018 American Psychiatric Association. All rights reserved.
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.
The E-Risk Study is funded by the Medical Research Council (G1002190) and the National Institute of Child Health and Human Development (HD077482). The Dunedin Longitudinal Study is funded by the New Zealand Health Research Council, the New Zealand Ministry of Business, Innovation, and Employment, the National Institute on Aging (AG032282), and the Medical Research Council (MR/P005918/1). Additional support was provided by a Distinguished Investigator Award from the American Asthma Foundation to Dr. Mill, and by the Jacobs Foundation and the Avielle Foundation. Dr. Marzi was funded by the EU-FP7 Marie Curie ITN EpiTrain (REA grant agreement no. 316758). Dr. Arseneault is the Mental Health Leadership Fellow for the U.K. Economic and Social Research Council. Dr. Fisher is supported by an MQ Fellows Award (MQ14F40). Dr. Odgers is a Jacobs Foundation and Canadian Institute for Advanced Research Fellow. Dr. Belsky is a Jacobs Foundation Fellow. This work used a high-performance computing facility partially supported by grant 2016-IDG-1013 (“HARDAC+: Reproducible HPC for Next-generation Genomics”) from the North Carolina Biotechnology Center. Dr. Pariante has received research funding from Johnson & Johnson and from a Wellcome-led consortium that includes Lundbeck, GlaxoSmithKline, and Pfizer, and he has served as a consultant for Lundbeck and Eleusis Benefit Corporation. The other authors report no financial relationships with commercial interests.
This is the author accepted manuscript. The final version is available from American Psychiatric Publishing via the DOI in this record.
Published online 12 January 2018