Obsessive-compulsive disorder, which genes? Which functions? Which pathways? An integrated holistic view regarding OCD and its complex genetic etiology

J Neurogenet. 2017 Sep;31(3):153-160. doi: 10.1080/01677063.2017.1336236. Epub 2017 Jun 13.

Abstract

Obsessive-compulsive disorder (OCD) is characterized by recurrent obtrusive and repetitive acts typically occurred following anxiety. In the last two decades, studies done on the gene sequences, large-scale and point mutations and gene-gene, gene-environment and gene-drug interactions have led to the discovery of hundreds of genes associated with OCD. Although each gene in turn is a part of the etiology of this disorder; however, OCD, like other mental disorders is complex and a comprehensive and integrated view is necessary to understand its genetic basis. In this study, through an extensive review of existing published studies, all genes associated with OCD were found. Then, in order to integrate the results, all the interactions between these genes were explored and the achievement was represented as an interactive genetic network. Furthermore, the reconstructed network was analyzed. It was found that GRIN2A, GRIN2B and GRIA2 are the most central nodes in the network. Functional and pathway enrichment analysis showed that glutamate-related pathways are the main deficient systems in patients with OCD. By studying genes shared between OCD and other diseases, it was cleared that OCD, epilepsy and some types of cancer have the most number of shared genes. The results of this study, in addition to reviewing the available results as a comprehensive and integrated manner, provide new hypotheses for future studies.

Keywords: Obsessive–compulsive disorder; functional enrichment analysis; gene; genetic network; pathway enrichment analysis.

Publication types

  • Review

MeSH terms

  • Female
  • Gene Regulatory Networks / genetics
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing
  • Humans
  • Male
  • Obsessive-Compulsive Disorder / etiology*
  • Obsessive-Compulsive Disorder / genetics*
  • Receptors, AMPA / genetics
  • Receptors, N-Methyl-D-Aspartate / genetics*

Substances

  • NR2B NMDA receptor
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • glutamate receptor ionotropic, AMPA 2
  • N-methyl D-aspartate receptor subtype 2A