TY - JOUR A1 - Rutten, BPF A1 - Vermetten, E A1 - Vinkers, CH A1 - Ursini, G A1 - Daskalakis, NP A1 - Pishva, E A1 - de Nijs, L A1 - Houtepen, LC A1 - Eijssen, L A1 - Jaffe, AE A1 - Kenis, G A1 - Viechtbauer, W A1 - van den Hove, D A1 - Schraut, KG A1 - Lesch, K-P A1 - Kleinman, JE A1 - Hyde, TM A1 - Weinberger, DR A1 - Schalkwyk, L A1 - Lunnon, K A1 - Mill, J A1 - Cohen, H A1 - Yehuda, R A1 - Baker, DG A1 - Maihofer, AX A1 - Nievergelt, CM A1 - Geuze, E A1 - Boks, MPM T1 - Longitudinal analyses of the DNA methylome in deployed military servicemen identify susceptibility loci for post-traumatic stress disorder JF - Molecular Psychiatry N2 - 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. KW - Molecular biology KW - Psychiatric disorders Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227171 VL - 23 IS - 5 ER - TY - JOUR A1 - Abu-Halima, Masood A1 - Häusler, Sebastian A1 - Backes, Christina A1 - Fehlmann, Tobias A1 - Staib, Claudia A1 - Nestel, Sigrun A1 - Nazarenko, Irina A1 - Meese, Eckart A1 - Keller, Andreas T1 - Micro-ribonucleic acids and extracellular vesicles repertoire in the spent culture media is altered in women undergoing \(In\) \(Vitro\) Fertilization JF - Scientific Reports N2 - MicroRNAs (miRNAs) are class of small RNA molecules with major impact on gene regulation. We analyzed the potential of miRNAs secreted from pre-implantation embryos into the embryonic culture media as biomarkers to predict successful pregnancy. Using microarray analysis, we profiled the miRNome of the 56 spent culture media (SCM) after embryos transfer and found a total of 621 miRNAs in the SCM. On average, we detected 163 miRNAs in SCM of samples with failed pregnancies, but only 149 SCM miRNAs of embryos leading to pregnancies. MiR-634 predicted an embryo transfer leading to a positive pregnancy with an accuracy of 71% and a sensitivity of 85%. Among the 621 miRNAs, 102 (16.4%) showed a differential expression between positive and negative outcome of pregnancy with miR-29c-3p as the most significantly differentially expressed miRNA. The number of extracellular vehicles was lower in SCM with positive outcomes (3.8 × 10\(^9\)/mL EVs), as compared to a negative outcome (7.35 × 10\(^9\)/mL EVs) possibly explaining the reduced number of miRNAs in the SCM associated with failed pregnancies. The analysis of the miRNome in the SCM of couples undergoing fertility treatment lays the ground towards development of biomarkers to predict successful pregnancy and towards understanding the role of embryonic miRNAs found in the SCM. KW - Medicine KW - miRNAs KW - Molecular biology KW - Non-coding RNAs Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173632 VL - 7 ER -