Introduction: Major depressive disorder (MDD) is a mental disorder caused by the combination of genetic, environmental, and psychological factors. Over the years, a number of genes potentially associated with MDD have been identified. However, in many cases, the role of these genes and their relationship in the etiology and development of MDD remains unclear. Under such situation, a systems biology approach focusing on the function correlation and interaction of the candidate genes in the context of MDD will provide useful information on exploring the molecular mechanisms underlying the disease.
Methods: We collected genes potentially related to MDD by screening the human genetic studies deposited in PubMed (https://www.ncbi.nlm.nih.gov/pubmed). The main biological themes within the genes were explored by function and pathway enrichment analysis. Then, the interaction of genes was analyzed in the context of protein-protein interaction network and a MDD-specific network was built by Steiner minimal tree algorithm.
Results: We collected 255 candidate genes reported to be associated with MDD from available publications. Functional analysis revealed that biological processes and biochemical pathways related to neuronal development, endocrine, cell growth and/or survivals, and immunology were enriched in these genes. The pathways could be largely grouped into three modules involved in biological procedures related to nervous system, the immune system, and the endocrine system, respectively. From the MDD-specific network, 35 novel genes potentially associated with the disease were identified.
Conclusion: By means of network- and pathway-based methods, we explored the molecular mechanism underlying the pathogenesis of MDD at a systems biology level. Results from our work could provide valuable clues for understanding the molecular features of MDD.
Keywords: major depressive disorder; network analysis; pathway cross talk.
© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.