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

Rutten, BPF and Vermetten, E and Vinkers, CH and Ursini, G and Daskalakis, NP and Pishva, E and de Nijs, L and Houtepen, LC and Eijssen, L and Jaffe, AE and Kenis, G and Viechtbauer, W and van den Hove, D and Schraut, KG and Lesch, K-P and Kleinman, JE and Hyde, TM and Weinberger, DR and Schalkwyk, L and Lunnon, K and Mill, J and Cohen, H and Yehuda, R and Baker, DG and Maihofer, AX and Nievergelt, CM and Geuze, E and Boks, MPM (2017) 'Longitudinal analyses of the DNA methylome in deployed military servicemen identify susceptibility loci for post-traumatic stress disorder.' Mol Psychiatry. ISSN 1476-5578

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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.Molecular Psychiatry advance online publication, 20 June 2017; doi:10.1038/mp.2017.120.

Item Type: Article
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Faculty of Science and Health > Biological Sciences, School of
Depositing User: Leonard Schalkwyk
Date Deposited: 27 Jun 2017 10:38
Last Modified: 17 Aug 2017 17:16

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