Effects of CPAP on the transcriptional signatures in patients with obstructive sleep apnea via coexpression network analysis.

Abstract

A growing number of studies provide epidemiological evidence linking obstructive sleep apnea (OSA) with a number of chronic disorders. Transcriptional analyses have been conducted to analyze the gene expression data. However, the weighted gene coexpression network analysis (WGCNA) method has not been applied to determine the transcriptional consequence of continuous positive airway pressure (CPAP) therapy in patients with severe OSA. The aim of this study was to identify key pathways and genes in patients with OSA that are influenced by CPAP treatment and uncover/unveil potential molecular mechanisms using WGCNA. We analyzed the microarray data of OSA (GSE 49800) listed in the Gene Expression Omnibus database. Coexpression modules were constructed using WGCNA. In addition, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were also conducted. After the initial data processing, 5101 expressed gene profiles were identified. Next, a weighted gene coexpression network was established and 16 modules of coexpressed genes were identified. The interaction analysis demonstrated a relative independence of gene expression in these modules. The black module, tan module, midnightblue module, pink module, and greenyellow module were significantly associated with the alterations in circulating leukocyte gene expression at baseline and after exposure to CPAP. The five hub genes were considered to be candidate OSA‐related genes after CPAP treatment. Functional enrichment analysis revealed that steroid biosynthesis, amino sugar and nucleotide sugar metabolism, protein processing in the endoplasmic reticulum, and the insulin signaling pathway play critical roles in the development of OSA in circulating leukocyte gene expression at baseline and after exposure to CPAP. Using this new systems biology approach, we identified several genes and pathways that appear to be critical to OSA after CPAP treatment, and these findings provide a better understanding of OSA pathogenesis.