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      A pilot investigation on DNA methylation modifications associated with complex posttraumatic symptoms in elderly traumatized in childhood

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          Abstract

          Objective

          Complex posttraumatic stress disorder (CPTSD) is a newly proposed diagnosis in the International Classification of Diseases-version 11, which is currently intensively investigated. Childhood trauma is regarded as main source of CPTSD symptoms, even in later life. Induction of DNA methylation changes by childhood trauma may contribute to its long-lasting adverse health consequences. The current study analyzed the correlation of genome-wide DNA methylation profiles with complex posttraumatic sequelae in buccal epithelial cells from 31 elderly former indentured child laborers (Verdingkinder) using the Infinium Illumina 450k Human DNA methylation chip.

          Results

          DNA methylation modifications indicated experiment-wide significant associations with the following complex posttraumatic symptom domains: dissociation, tension reduction behavior and dysfunctional sexual behavior. Differentially methylated CpG sites were mapped to the genes huntington associated protein 1 ( HAP1), RAN binding protein 2 ( RANBP2) and proteasome subunit alpha 4 ( PSMA4), respectively. In addition, the methylation of cg07225277 located in carnosine synthase 1 ( CARNS1) correlated with trauma symptom complexity. Our pilot data suggest correlation of DNA methylation modifications with complex posttraumatic symptoms in elderly individuals subjected to prolonged and complex childhood trauma. More comprehensive and elaborated studies should be carried out to analyze epigenetic modifications associated with CPTSD.

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          Most cited references23

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          High density DNA methylation array with single CpG site resolution.

          We have developed a new generation of genome-wide DNA methylation BeadChip which allows high-throughput methylation profiling of the human genome. The new high density BeadChip can assay over 480K CpG sites and analyze twelve samples in parallel. The innovative content includes coverage of 99% of RefSeq genes with multiple probes per gene, 96% of CpG islands from the UCSC database, CpG island shores and additional content selected from whole-genome bisulfite sequencing data and input from DNA methylation experts. The well-characterized Infinium® Assay is used for analysis of CpG methylation using bisulfite-converted genomic DNA. We applied this technology to analyze DNA methylation in normal and tumor DNA samples and compared results with whole-genome bisulfite sequencing (WGBS) data obtained for the same samples. Highly comparable DNA methylation profiles were generated by the array and sequencing methods (average R2 of 0.95). The ability to determine genome-wide methylation patterns will rapidly advance methylation research. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Epigenome-wide association studies for common human diseases.

            Despite the success of genome-wide association studies (GWASs) in identifying loci associated with common diseases, a substantial proportion of the causality remains unexplained. Recent advances in genomic technologies have placed us in a position to initiate large-scale studies of human disease-associated epigenetic variation, specifically variation in DNA methylation. Such epigenome-wide association studies (EWASs) present novel opportunities but also create new challenges that are not encountered in GWASs. We discuss EWAS design, cohort and sample selections, statistical significance and power, confounding factors and follow-up studies. We also discuss how integration of EWASs with GWASs can help to dissect complex GWAS haplotypes for functional analysis.
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              A language and environment for statistical computing

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                Author and article information

                Contributors
                zoyamarinova@gmail.com
                maercker@psychologie.uzh.ch
                edna.gruenblatt@kjpd.uzh.ch
                wojdacz@biomed.au.dk
                susanne.walitza@puk.zh.ch
                Journal
                BMC Res Notes
                BMC Res Notes
                BMC Research Notes
                BioMed Central (London )
                1756-0500
                19 December 2017
                19 December 2017
                2017
                : 10
                : 752
                Affiliations
                [1 ]ISNI 0000 0004 1937 0650, GRID grid.7400.3, Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, , University of Zurich, ; Zurich, Switzerland
                [2 ]ISNI 0000 0004 1937 0650, GRID grid.7400.3, Department of Psychology, Division of Psychopathology and Clinical Intervention, , University of Zurich, ; Binzmühlerstrasse 14/17, Raum BIN 3 E 14, 8050 Zurich, Switzerland
                [3 ]ISNI 0000 0001 1956 2722, GRID grid.7048.b, Aarhus Institute of Advanced Studies, , University of Aarhus, ; Aarhus, Denmark
                Article
                3082
                10.1186/s13104-017-3082-y
                5738217
                29258561
                487269cc-91ad-4cb1-89a6-6de17583a9a2
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 March 2017
                : 12 December 2017
                Categories
                Research Note
                Custom metadata
                © The Author(s) 2017

                Medicine
                childhood trauma,complex posttraumatic stress disorder,dna methylation,epigenetic modifications

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