# Identification and Mendelian randomization validation of pathogenic gene biomarkers in obstructive sleep apnea

## TL;DR

This study identifies key genes linked to obstructive sleep apnea and confirms their causal role using genetic data, offering new insights into its biology.

## Contribution

The study uses WGCNA and Mendelian randomization to identify and validate causal genes in obstructive sleep apnea.

## Key findings

- 194 differentially expressed genes were identified in obstructive sleep apnea.
- CETN3 and GTF2A2 were confirmed as causally linked to obstructive sleep apnea through Mendelian randomization.
- Immune cell populations like memory B cells and M0 macrophages showed significant alterations in OSA.

## Abstract

By 2020, obstructive sleep apnea (OSA), a prevalent respiratory disorder, had affected 26.6–43.2% of males and 8.7–27.8% of females worldwide. OSA is associated with conditions such as hypertension, diabetes, and tumor progression; however, the precise underlying pathways remain elusive. This study aims to identify genetic markers and molecular mechanisms of OSA to improve understanding and treatment strategies.

The GSE135917 dataset related to OSA was obtained from the GEO database. Differentially expressed genes (DEGs) were subsequently identified. Weighted gene co-expression network analysis (WGCNA) was conducted to pinpoint disease-associated genes. The intersection of these data enabled the identification of potential diagnostic DEGs. Further analyses included Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment studies, exploration of protein–protein interactions based on these genes, and an examination of immune infiltration. Mendelian randomization was employed to validate core genes against the Genome-Wide Association Study database.

A total of 194 DEGs were identified in this study. WGCNA network analysis highlighted 2,502 DEGs associated with OSA. By intersecting these datasets, 53 diagnostic DEGs primarily involved in metabolic pathways were identified. Significant alterations were observed in immune cell populations, including memory B cells, plasma cells, naive CD4 T cells, M0 macrophages, and activated dendritic cells. CETN3, EEF1E1, PMM2, GTF2A2, and RRM2 emerged as hub genes implicated in the pathogenesis. A line graph model provides diagnostic insights. Mendelian randomization analysis confirmed a causal link between CETN3 and GTF2A2 with OSA.

Through WGCNA, this analysis uncovered significant genetic foundations of OSA, identifying 2,502 DEGs and 194 genes associated with the disorder. Among these, CETN3 and GTF2A2 were found to have causal relationships with OSA.