Biomarker-Based Analysis of the Association Between Obstructive Sleep Apnea Syndrome and Oxidative Stress: A Univariable, Bidirectional, and Multivariable Mendelian Randomization Study.

OBJECTIVE

This study aimed to investigate the potential genetic association between obstructive sleep apnea syndrome (OSAS) and oxidative stress (OS) using multi- -dimensional Mendelian randomization (MR) analysis.

METHODS

We conducted bidirectional univariable MR analyses using FinnGen-derived OSAS genetic data and summary statistics for 16 oxidative stress biomarker indicators (OSBIs) from IEU OpenGWAS and GWAS Catalog, employing five methods with sensitivity analyses to evaluate robustness and heterogeneity. Multivariable MR (MVMR) was further applied to adjust for confounders and estimate the direct effect of OSAS on OSBIs.

RESULTS

OSAS might be a risk factor for elevated lactate (OR = 1.06, 95% CI = 1.02-1.11, p < 0.01). MVMR supported an independent causal effect (OR = 1.16, 95% CI = 1.02-1.32, p = 0.03), although significant heterogeneity suggests interpretation requires caution. Reverse MR suggested that decreased superoxide dismutase (OR = 0.96, 95% CI = 0.93-0.98, p < 0.01) and matrix metalloproteinase-9 (OR = 0.98, 95% CI = 0.96-0.99, p < 0.01) were associated with OSAS. Furthermore, MVMR suggested a potential effect of OSAS on elevated vitamin E levels (OR = 1.15, 95% CI = 1.01-1.32, p = 0.04).

DISCUSSION: Our study provides genetic evidence for a bidirectional causal relationship between OSAS and OSBIs. Potential mechanisms may include hypoxia-disordered glucose metabolism and a compensatory upregulation of the antioxidant system. Future research should utilize larger, multi-ethnic samples and incorporate a broader range of OSBIs to systematically delineate these relationships.

CONCLUSION

OS is both a driver and a pathological consequence of OSAS.