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Mol Psychiatry. 2018 May;23(5):1145-1156. doi: 10.1038/mp.2017.120. Epub 2017 Jun 20.

Longitudinal analyses of the DNA methylome in deployed military servicemen identify susceptibility loci for post-traumatic stress disorder.

Author information

1
School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands.
2
Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
3
Research Centre for Military Mental Healthcare, Ministry of Defence, Utrecht, The Netherlands.
4
Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
5
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
6
Department of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai and Mental Health Patient Care Center, James J. Peters Veterans Affairs Medical Center, New York, NY, USA.
7
Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
8
Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, USA.
9
Department of Neurology and Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA.
10
Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
11
Molecular and Cellular Biosciences Research Group, University of Essex, Colchester, UK.
12
University of Exeter Medical School, Exeter University, Exeter, UK.
13
Anxiety and Stress Research Unit, Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
14
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
15
VA Center of Excellence for Stress and Mental Health, San Diego, CA, USA.
16
Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.

Abstract

In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions. Evidence for mediation of the relation between combat trauma and PTSD symptoms by longitudinal changes in DNA methylation was observed at several positions and regions. Bioinformatic analyses of the reported associations identified significant enrichment in several pathways relevant for symptoms of PTSD. Targeted analyses of the significant findings from the discovery sample in an independent prospective cohort of male US marines (n=98) replicated the observed relation between decreases in DNA methylation levels and PTSD symptoms at genomic regions in ZFP57, RNF39 and HIST1H2APS2. Together, our study pinpoints three novel genomic regions where longitudinal decreases in DNA methylation across the period of exposure to combat trauma marks susceptibility for PTSD.

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