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Identification of Hub Genes and Key Pathways Associated With Bipolar Disorder Based on Weighted Gene Co-expression Network Analysis

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Identification of Hub Genes and Key Pathways Associated With Bipolar Disorder Based on Weighted Gene Co-expression Network Analysis

Yang Liu et al. Front Physiol.

Abstract

Bipolar disorder (BD) is a complex mental disorder with high mortality and disability rates worldwide; however, research on its pathogenesis and diagnostic methods remains limited. This study aimed to elucidate potential candidate hub genes and key pathways related to BD in a pre-frontal cortex sample. Raw gene expression profile files of GSE53987, including 36 samples, were obtained from the gene expression omnibus (GEO) database. After data pre-processing, 10,094 genes were selected for weighted gene co-expression network analysis (WGCNA). After dividing highly related genes into 19 modules, we found that the pink, midnight blue, and brown modules were highly correlated with BD. Functional annotation and pathway enrichment analysis for modules, which indicated some key pathways, were conducted based on the Enrichr database. One of the most remarkable significant pathways is the Hippo signaling pathway and its positive transcriptional regulation. Finally, 30 hub genes were identified in three modules. Hub genes with a high degree of connectivity in the PPI network are significantly enriched in positive regulation of transcription. In addition, the hub genes were validated based on another dataset (GSE12649). Taken together, the identification of these 30 hub genes and enrichment pathways might have important clinical implications for BD treatment and diagnosis.

Keywords: WGCNA; bipolar disorder; hub genes; modules; pre-frontal cortex.

Figures

FIGURE 1
FIGURE 1
Module-trait relationships. Stage indicated bipolar disorder (BD) and non-BD.
FIGURE 2
FIGURE 2
Scatter diagram for module membership vs. gene significance of stage (BD or non-BD) in three modules.
FIGURE 3
FIGURE 3
PPI network for all candidate modules.
FIGURE 4
FIGURE 4
Boxplot for identification of hub genes in the three modules.

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