Identification of key genes in late-onset major depressive disorder through a co-expression network module

Abstract

Late-onset major depressive disorder (LOD) increases the risk of disability and suicide in elderly patients. However, the complex pathological mechanism of LOD still remains unclear. We selected 10 LOD patients and 12 healthy control samples from the GSE76826 dataset for statistical analysis. Under the screening criteria, 811 differentially expressed genes (DEGs) were screened. We obtained a total of two most clinically significant modules through the weighted gene co-expression network analysis (WGCNA). Functional analysis of the genes in the most clinically significant modules was performed to explore the potential mechanism of LOD, followed by protein–protein interaction (PPI) analysis and hub gene identification in the core area of the PPI network. Furthermore, we identified immune infiltrating cells using the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm between healthy subjects and LOD patients with the GSE98793 dataset. Next, six hub genes (CD27, IL7R, CXCL1, CCR7, IGLL5, and CD79A) were obtained by intersecting hub genes with DEGs, followed by verifying the diagnostic accuracy with the receiver operating characteristic curve (ROC). In addition, we constructed the least absolute shrinkage and selection operator (LASSO) regression model for hub gene cross-validation. Finally, we found that CD27 and IGLL5 were good diagnostic indicators of LOD, and CD27 may be the key gene of immune function change in LOD. In conclusion, our research shows that the changes in the immune function may be an important mechanism in the development of LOD, which can provide some guidance for the related research of LOD in the future.

Integrated analysis of transcriptional changes in major depressive disorder: Insights from blood and anterior cingulate cortex

“…Previously, the association between the CD79A and MDD was few explored. Yao et al found that CD79A could be used as the accurate diagnostic indicators of late-onset MDD [ 63 ], while the molecular mechanism deserved further exploration.…”

Transcriptomic analysis of mRNAs in human whole blood identified age-specific changes in healthy individuals

“…[20][21][22] Although the mutation rate of IGLL5 did not change with age, [23] Yao et al have shown that the low expression level of IGLL5 is a good diagnostic in elderly patients with late-onset major depressive disorder which increases the risk of suicide and disability in olds. [24] Therefore, we speculated that IGLL5 has a vital role in staying healthy for elders. Our study found that IGLL5 showed a down-regulated level in elders with a great ROC score (AUC value > 0.7), further illustrating the potential of IGLL5 as a biomarker of health for elders.…”