D Mehta1, D Bruenig2,3, T Carrillo-Roa4, B Lawford2, W Harvey3, C P Morris2, A K Smith5,6,7, E B Binder4,7, R McD Young8, J Voisey2. 1. School of Psychology and Counselling, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia. 2. School of Biomedical Sciences, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia. 3. Gallipoli Medical Research Institute, Greenslopes Private Hospital, Greenslopes, QLD, Australia. 4. Department of Translational Research, Max Planck Institute of Psychiatry, Munich, Germany. 5. Genetics and Molecular Biology Program, Emory University, Atlanta, GA, USA. 6. Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA. 7. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. 8. Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia.
Abstract
OBJECTIVE: Epigenetic modifications such as DNA methylation may play a key role in the aetiology and serve as biomarkers for post-traumatic stress disorder (PTSD). We performed a genomewide analysis to identify genes whose DNA methylation levels are associated with PTSD. METHOD: A total of 211 individuals comprising Australian male Vietnam War veterans (n = 96) and males from a general population belonging to the Grady Trauma Project (n = 115) were included. Genomewide DNA methylation was performed from peripheral blood using the Illumina arrays. Data analysis was performed using generalized linear regression models. RESULTS: Differential DNA methylation of 17 previously reported PTSD candidate genes was associated with PTSD symptom severity. Genomewide analyses revealed CpG sites spanning BRSK1, LCN8, NFG and DOCK2 genes were associated with PTSD symptom severity. We replicated the findings of DOCK2 in an independent cohort. Pathway analysis revealed that among the associated genes, genes within actin cytoskeleton and focal adhesion molecular pathways were enriched. CONCLUSION: These data highlight the role of DNA methylation as biomarkers of PTSD. The results support the role of previous candidates and uncover novel genes associated with PTSD, such as DOCK2. This study contributes to our understanding of the biological underpinnings of PTSD.
OBJECTIVE: Epigenetic modifications such as DNA methylation may play a key role in the aetiology and serve as biomarkers for post-traumatic stress disorder (PTSD). We performed a genomewide analysis to identify genes whose DNA methylation levels are associated with PTSD. METHOD: A total of 211 individuals comprising Australian male Vietnam War veterans (n = 96) and males from a general population belonging to the Grady Trauma Project (n = 115) were included. Genomewide DNA methylation was performed from peripheral blood using the Illumina arrays. Data analysis was performed using generalized linear regression models. RESULTS: Differential DNA methylation of 17 previously reported PTSD candidate genes was associated with PTSD symptom severity. Genomewide analyses revealed CpG sites spanning BRSK1, LCN8, NFG and DOCK2 genes were associated with PTSD symptom severity. We replicated the findings of DOCK2 in an independent cohort. Pathway analysis revealed that among the associated genes, genes within actin cytoskeleton and focal adhesion molecular pathways were enriched. CONCLUSION: These data highlight the role of DNA methylation as biomarkers of PTSD. The results support the role of previous candidates and uncover novel genes associated with PTSD, such as DOCK2. This study contributes to our understanding of the biological underpinnings of PTSD.
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