Exploring the Causal Effect of Mitochondrial DNA Copy Number on Obstructive Sleep Apnea.

PURPOSE: Although some studies have established a clear association between mitochondrial DNA (mtDNA) copy number and obstructive sleep apnea (OSA), the causative relationship between the two remains unclear, which is what this study aims to explore.

METHOD: We investigated the causal relationship between mtDNA copy number and OSA based on public genome-wide association study data utilizing a two-sample Mendelian randomization (MR) analysis and also explored the mediating role of immune cells between the two using a mediator MR analysis. We estimated the causal effects primarily using the inverse variance weighted method and conducted sensitivity analyses based on the MR-Egger intercept method and Cochran's Q test.

FINDING: We found that mtDNA copy number had a significant negative causal effect on OSA (odd ratio [OR] [95% confidence interval (CI)] = 0.844 [0.778-0.911], p = 0.03), whereas OSA did not have a causal effect on mtDNA copy number (OR [95% CI] = 0.995 [0.979-1.01], p = 0.791). We identified that the terminally differentiated CD4-CD8- T cell Absolute Count met the requirements for mediation analysis (OR [95% CI]as exposure = 0.989 [0.985-0.993], p = 0.016, OR[95% CI]as outcome = 0.717 [0.529-0.973], p = 0.033). Under this condition, the mediation effect size of the immune cell was 0.003, which is considered to have no mediating effect either using the bootstrap method or the two-step method (p > 0.05).

CONCLUSION

Our study indicates that reducing mtDNA copy numbers is a risk factor for the development of OSA, rather than a consequence of it. Improving mitochondrial dysfunction may help prevent or treat OSA.