Prediction of Possible Biomarkers and Novel Pathways Conferring Risk to Post-Traumatic Stress Disorder

PLoS One. 2016 Dec 20;11(12):e0168404. doi: 10.1371/journal.pone.0168404. eCollection 2016.

Abstract

Post-traumatic stress disorder is one of the common mental ailments that is triggered by exposure to traumatic events. Till date, the molecular factors conferring risk to the development of PTSD is not well understood. In this study, we have conducted a meta-analysis followed by hierarchical clustering and functional enrichment, to uncover the potential molecular networks and critical genes which play an important role in PTSD. Two datasets of expression profiles from Peripheral Blood Mononuclear Cells from 62 control samples and 63 PTSD samples were included in our study. In PTSD samples of GSE860 dataset, we identified 26 genes informative when compared with Post-deploy PTSD condition and 58 genes informative when compared with Pre-deploy and Post-deploy PTSD of GSE63878 dataset. We conducted the meta-analysis using Fisher, roP, Stouffer, AW, SR, PR and RP methods in MetaDE package. Results from the rOP method of MetaDE package showed that among these genes, the following showed significant changes including, OR2B6, SOX21, MOBP, IL15, PTPRK, PPBPP2 and SEC14L5. Gene ontology analysis revealed enrichment of these significant PTSD-related genes for cell proliferation, DNA damage and repair (p-value ≤ 0.05). Furthermore, interaction network analysis was performed on these 7 significant genes. This analysis revealed highly connected functional interaction networks with two candidate genes, IL15 and SEC14L5 highly enriched in networks. Overall, from these results, we concluded that these genes can be recommended as some of the potential targets for PTSD.

MeSH terms

  • Biomarkers / metabolism
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics
  • Databases, Genetic*
  • Gene Expression Regulation*
  • Gene Regulatory Networks*
  • Humans
  • Interleukin-15 / biosynthesis*
  • Interleukin-15 / genetics
  • Leukocytes, Mononuclear / metabolism*
  • Stress Disorders, Post-Traumatic / genetics
  • Stress Disorders, Post-Traumatic / metabolism*

Substances

  • Biomarkers
  • Carrier Proteins
  • IL15 protein, human
  • Interleukin-15