Obstructive Sleep Apnea Associated with Periodontitis: Evidence from Mendelian Randomization and Salivary Proteomics

Clinical evidence supports a link between obstructive sleep apnea (OSA) and periodontitis. However, whether OSA exerts a causal effect on periodontitis and the underlying protein biomarkers remains unclear. This study aimed to investigate their causal relationship and to identify salivary protein markers involved in the shared pathogenesis. First, a bidirectional two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) statistics was conducted to evaluate the causal relationship. Second, data-independent acquisition (DIA)-based salivary proteomics was applied to identify differentially expressed proteins in periodontally healthy patients with OSA (<i>n</i> = 30) and controls (<i>n</i> = 10). The OSA-associated upregulated proteins were screened for consistency with OSA severity and overlap with an independent periodontitis cohort. Network and hub protein analyses were performed. Genetic analysis in the MR suggested that OSA could statistically contribute to periodontitis development, but not in the reverse direction. Salivary proteomics revealed severity-dependent expression changes in OSA, with upregulated proteins enriched in the antigen processing and presentation pathway. Eight proteins detected in OSA patients showed increased expression with periodontal destruction. NAMPT, GSN, and S100A8/A9 emerged as hub proteins, validated by ELISA in independent OSA-associated periodontitis patients. The integrative genetic and proteomic investigations support a potential causal and proteome association between OSA and periodontitis, highlighting NAMPT, GSN, and S100A8/A9 as candidate mediators that may underpin the inflammatory interplay.