Characterization of Whole Genome DNA Methylation Profile Associated with Post-Traumatic Stress Disorder in OIF/OEF Veterans [bisulfite-converted DNA]

ABSTRACT: Emerging knowledge suggests that post-traumatic stress disorder (PTSD) is causally associated with epigenetic changes although its molecular underpinnings are still largely elusive. We postulate that differentially methylated probes mined from peripheral whole blood could be candidates for potential PTSD diagnostic signatures. Working within the Systems Biology PTSD Biomarker Consortium (SBPBC), we investigated a training set comprising of 48 PTSD male veterans (CAPS > 40) and 51 age/ethnicity matched controls (CAPS < 20). Agilent whole genome array detected ~5,600 differentially methylated CpG islands (CpGI) annotated to ~2,800 differentially methylated genes (DMG). The majority (84.5%) of these DMGs was hypermethylated in PTSD veterans. Thereof ~30% promoter-bound DMGs were used for functional analysis. Taking cues from the clinical information, the curated networks were enlisted into four major clusters, namely PTSD-associated complications, PTSD-relevant endocrine signaling, nervous system development and nervous system functions. Enduring impacts of PTSD was manifested by differentially methylated genes enriching networks associated with LTP, fear memory architecture and complications linked to insulin resistance and innate immunity. These networks were further validated by an independent test set comprising of 31/29 PTSD+/- veteran selected using aforementioned screening protocol. Two independent assay platforms presented technical validations. Probing the combined 83/83 PTSD+/- cohort, whole genome array from Illumina, Inc. validated most of the networks of interest. Methylation statuses of eight DMGs relevant to PTSD and comorbidities were confirmed by targeted bisulfite sequencing. This list presents a potential set of PTSD biomarkers of translational potential.

ORGANISM(S): Homo sapiens

PROVIDER: GSE89218 | GEO | 2019/09/01

REPOSITORIES: GEO