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Meta-Analysis
. 2018 Jun:92:123-134.
doi: 10.1016/j.psyneuen.2017.12.007. Epub 2017 Dec 27.

Traumatic stress and accelerated DNA methylation age: A meta-analysis

Erika J Wolf  1 , Hannah Maniates  2 , Nicole Nugent  3 , Adam X Maihofer  4 , Don Armstrong  5 , Andrew Ratanatharathorn  6 , Allison E Ashley-Koch  7 , Melanie Garrett  8 , Nathan A Kimbrel  9 , Adriana Lori  10 , Va Mid-Atlantic Mirecc Workgroup  11 , Allison E Aiello  12 , Dewleen G Baker  13 , Jean C Beckham  9 , Marco P Boks  14 , Sandro Galea  15 , Elbert Geuze  16 , Michael A Hauser  7 , Ronald C Kessler  17 , Karestan C Koenen  18 , Mark W Miller  19 , Kerry J Ressler  20 , Victoria Risbrough  13 , Bart P F Rutten  21 , Murray B Stein  22 , Robert J Ursano  23 , Eric Vermetten  24 , Christiaan H Vinkers  14 , Monica Uddin  25 , Alicia K Smith  26 , Caroline M Nievergelt  13 , Mark W Logue  27
Affiliations
Meta-Analysis

Traumatic stress and accelerated DNA methylation age: A meta-analysis

Erika J Wolf et al. Psychoneuroendocrinology. 2018 Jun.

Abstract

Background: Recent studies examining the association between posttraumatic stress disorder (PTSD) and accelerated aging, as defined by DNA methylation-based estimates of cellular age that exceed chronological age, have yielded mixed results.

Methods: We conducted a meta-analysis of trauma exposure and PTSD diagnosis and symptom severity in association with accelerated DNA methylation age using data from 9 cohorts contributing to the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (combined N = 2186). Associations between demographic and cellular variables and accelerated DNA methylation age were also examined, as was the moderating influence of demographic variables.

Results: Meta-analysis of regression coefficients from contributing cohorts revealed that childhood trauma exposure (when measured with the Childhood Trauma Questionnaire) and lifetime PTSD severity evidenced significant, albeit small, meta-analytic associations with accelerated DNA methylation age (ps = 0.028 and 0.016, respectively). Sex, CD4T cell proportions, and natural killer cell proportions were also significantly associated with accelerated DNA methylation age (all ps < 0.02). PTSD diagnosis and lifetime trauma exposure were not associated with advanced DNA methylation age. There was no evidence of moderation of the trauma or PTSD variables by demographic factors.

Conclusions: Results suggest that traumatic stress is associated with advanced epigenetic age and raise the possibility that cells integral to immune system maintenance and responsivity play a role in this. This study highlights the need for additional research into the biological mechanisms linking traumatic stress to accelerated DNA methylation age and the importance of furthering our understanding of the neurobiological and health consequences of PTSD.

Keywords: Accelerated aging; DNA methylation; Epigenetic clock; Meta-analysis; PTSD; Traumatic stress.

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Figures

Figure 1
Figure 1
shows the relationship between variance in each study in chronological age and the magnitude of the correlation between chronological age and Horvath and Hannum DNAm age estimates (linked via barbell for each study).
Figure 2
Figure 2
shows the forest plots for the significant meta-analytic associations between Hannum (left panel) and Horvath (right panel) DNAm age residuals and demographic and cellular variables. Error bars represent 95% confidence intervals. Study abbreviations are defined in Table 1.
Figure 3
Figure 3
shows the forest plots for the significant meta-analytic associations between childhood trauma (top panel) and lifetime PTSD severity (bottom panel) and Hannum DNAm age residuals. Error bars represent 95% confidence intervals. Study abbreviations are defined in Table 1.
See this image and copyright information in PMC

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