Transcriptomic and Polysomnographic Insights Into Core Signaling Pathways in Obstructive Sleep Apnea

Background: This study integrates transcriptomics and polysomnography (PSG) to investigate the core signaling pathways underlying obstructive sleep apnea (OSA), aiming to elucidate its complex pathophysiological mechanisms. These findings may provide new perspectives on the prevention, diagnosis, and treatment of OSA. Methods: Participants underwent PSG to monitor indicators, such as total sleep time, apnea-hypopnea index (AHI), oxygen desaturation index (ODI) and lowest oxygen saturation (LSO₂). Individuals with AHI > 5 were categorised into the OSA group, while others were classified as the regular snoring group. Total RNA from white blood cells was extracted using the TRIzol method, and transcriptomic data were obtained via high-throughput sequencing. Weighted Gene Coexpression Network Analysis (WGCNA) and Protein-Protein Interaction (PPI) network analysis were used to identify OSA-related core genes. Differential gene expression, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore key signaling pathways. Single-cell sequencing validated the findings, and Mendelian randomization (MR) analysis confirmed causal links between genes and pathways. Results: While no significant differences were observed between the OSA and regular snoring groups in gender, age, or body mass index (BMI), significant disparities were noted in sleep parameters such as AHI, ODI, and LSO₂. Principal component analysis (PCA) revealed transcriptomic differences between the groups. WGCNA identified 302 differentially expressed genes (DEGs), with the Palevioletred module significantly correlating with PSG parameters. GO and KEGG analyses implicated core genes in regulating inflammation, viral defence, cell growth, and apoptosis, highlighting the NF-κB signaling pathway as central to OSA pathogenesis. PPI analysis identified key genes, including CEBPB and SPI1, while single-cell sequencing suggested NF-κB pathway activation affecting T cell subgroup distribution. MR confirmed causal relationships between core genes and the NF-κB pathway. Conclusion: This study identified significant differences in sleep parameters between OSA and regular snoring groups and revealed core genes enriched in the NF-κB signaling pathway. These findings suggest that targeting the NF-κB pathway may offer therapeutic benefits for OSA.