WGCNA Identification of Genes and Pathways Involved in the Pathogenesis of Postmenopausal Osteoporosis.

PURPOSE: Postmenopausal osteoporosis (PMO) patients may suffer from chronic pain and increased fractures due to brittle bones that seriously affect their normal work and life. Exploring the pathogenesis of PMO can help clinicians construct individualized therapeutic targets.

METHODS

Differentially expressed genes (DEGs) were identified by analyzing the microarray assays of monocytes from 20 PMO and 20 control samples. Weighted correlation network analysis (WGCNA) and gene set enrichment analysis (GAEA) were performed. Genes associated with PMO were identified in the Comparative Toxicogenomics Database (CTD). miRNAs associated with osteoporosis were found in miRNet, and target genes were predicted. Hub genes and functional pathways associated with PMO were also identified. miRNA-mRNA networks were constructed. The association between hub genes and PMO was analyzed in the CTD.

RESULTS

A total of 1055 genes were up-regulated, and 694 genes were down-regulated in PMO samples (P<0.01). Five modules were identified by WGCNA. The blue module was significantly associated with PMO and selected for further analysis (P < 0.05). A total of 229 genes were significantly associated with PMO gene significance and module membership. Pathway variations were predominantly enriched in mRNA metabolic process, RNA splicing, Notch signaling pathway, apoptosis, cytokine-cytokine receptor interaction and so on. We identified 10 hub genes associated with PMO with different inference scores.

CONCLUSION

We identified genes, miRNAs, and pathways associated with PMO. These molecules may participate in the pathogenesis of PMO and serve as therapeutic targets.