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Characterization of the Epigenomic Status of the US OEF/OIF War Veterans: A Pilot Clinical Study
Author(s) -
Chakraborty Nabarun,
Muhie Seid,
Yang Ruoting,
Gautam Aarti,
Donohue Duncan,
Daigel Bernie,
Zhang Yuanyang,
Amara Duna Abu,
Flory Jannie,
Yehuda Rachel,
Doyle Frank,
Hammamieh Rasha,
Marmar Charles,
Jett Marti
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.831.3
Subject(s) - dna methylation , epigenetics , epigenomics , biomarker , methylated dna immunoprecipitation , methylation , gene , medicine , bioinformatics , biology , genetics , gene expression
Management of post‐traumatic stress disorder (PTSD) is complicated by the overlapping symptoms of its co morbidities and the diagnostic reliance on self‐report and time consuming psychological evaluation. A more comprehensive understanding of molecular pathophysiology of PTSD could facilitate an unbiased biomarker‐driven next‐generation intervention strategy. Herein, we cast light on the epigenomic consequences of combat elicited PTSD. In this study, hypermethylated genes were investigated as to the implications for behavior, immune response, nervous system development, and relevant PTSD co‐morbidities such as cardiac health and diabetes. 52 PTSD‐positive male veterans of US Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) were matched to 52 controls by age and ethnicity. PTSD diagnosis was determined by a clinician‐administered PTSD scale (CAPS), score >40, while the control group demonstrated a CAPS <10. Methylation status of DNA extracted from whole blood was assayed using high density arrays (Agilent, Inc.). 5,000 probes were statistically differentially methylated (FDR < 0.1), representing approximately 3,600 unique genes. Chromosome 4 and 18 imprints a significantly large portion of the methylated probes, including those which control emotional and cognition process, and glucocorticoid deficiency. Interestingly, a significant number of genes facilitating telomere maintenance and insulin reception were hypermethylated at both promoter and gene body sites; therefore the DNA methylation status in these genes could be prevailing. Nearly 85% of the differentially methylatedprobes were hypermethylated in PTSD patients. The majority of these probes encode the candidate proteins responsible for transcription regulation and enzymaticactions. Genes involved in memory consolidation, emotion/aggressive behavior, and perturbed circadian rhythm were preferentially hypermethylated. PTSD epigenetically perturbed both the cellular and humoral immune system; in addition the morphologies of two brain regions known to control PTSD symptoms, namely cerebral cortex and hippocampus were perturbed. Genes involved in several PTSD comorbidities, such as cardiomyopathy and poor insulin management, were also hypermethylated. Integration of the epigenomic observations with other omics outcomes is underway, as well as validation of these findings in an independent cohort.