Identification of differentially expressed gene modules in major depressive disorder based on weighted gene co-expression network analysis

doi:10.3969/j.issn.1674-8115.2021.06.004

Abstract

Abstract: Objective

·To explore the differential gene modules and hub genes of major depressive disorder (MDD) by weighted gene co-expression network analysis (WGCNA), and annotate the biological functions of the differential gene modules.

Methods

·Based on the previous experiment of peripheral blood mRNA microarray analysis of 8 MDD patients and 8 healthy controls (control group), t-test statistical method was used to screen the differentially expressed genes between MDD and the control group. WGCNA package in R software was used to analyze the weighted gene co-expression network. The correlation coefficient threshold was set to 0.9 with β =14 to construct the co-expression network of the gene dataset. The hybrid dynamic tree cutting method was used to cut the network to generate gene modules. Pearson correlation test was used to evaluate the correlation between gene modules and MDD. The gene modules with the strongest positive correlation and the strongest negative correlation with depression were selected respectively, and the top three genes with the highest connectivity in the modules were defined as hub genes. Finally, GO functional enrichment analysis and KEGG pathway analysis were used to annotate the functions of the two modules.

Results

·A total of 4 125 differentially expressed genes were obtained from 16 samples, and 9 gene modules were identified. The blue module (R=-0.91, P=0.000) and the cyan module (R=0.76, P=0.000) were selected for further study. The hub genes of blue module were JAM2 (junctional adhesion molecule 2), SCRN2 (secernin 2) and IGHV7-81 (immunoglobulin heavy variable 7-81). The hub genes of cyan module were SCFD2 (Sec1 family domain containing 2), NR5A2 (nuclear receptor subfamily 5 group A member 2) and KCNMA1 (potassium calcium-activated channel subfamily M alpha 1). It was found in the annotation of biological function that the genes of the cyan module were mainly enriched in the embryo development, cell growth and immune and inflammatory response, while the genes of the blue module were mainly enriched in material processing and transport and infection.

Conclusion

·Two peripheral blood mRNA gene modules and six hub genes (JAM2, SCRN2, IGHV7-81, SCFD2, NR5A2 and KCNMA1) may be significantly associated with MDD. These two gene modules may play a role in the embryonic development, immune and inflammatory response, and material processing and transportation.

Key words: major depressive disorder (MDD), weighted gene co-expression network analysis (WGCNA), differentially expressed gene (DEG), hub gene

CLC Number:

R749.4

Rui-jie GENG, Lin YAO, Xin-xin HUANG, Shun-ying YU, Cheng-mei YUAN, Wu HONG, Qin-yu LÜ, Qing-zhong WANG, Zheng-hui YI, Yi-ru FANG. Identification of differentially expressed gene modules in major depressive disorder based on weighted gene co-expression network analysis[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(6): 724-731.

Figures/Tables 5

Fig 1 Dendrogram of gene clustering

Fig 2 The association between 9 MEs of gene modules and depression

Fig 3 Gene interaction network of the blue module

Fig 4 Gene interaction network of the cyan module

Fig 5 Biological annotation of blue module and cyan module

TrendMD

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