Ji Ping, Fan Yujiang, Li Junling, Deng Zhaoan, Zhang Guofu, Du Jianbin
Department of Geriatric Psychiatry, The Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, China.
Department of Mental Health, People's Hospital of Huantai County, Zibo, China.
Brain Behav. 2025 Aug;15(8):e70720. doi: 10.1002/brb3.70720.
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.
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.
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] = 0.989 [0.985-0.993], p = 0.016, OR[95% CI] 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).
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.
尽管一些研究已明确线粒体DNA（mtDNA）拷贝数与阻塞性睡眠呼吸暂停（OSA）之间存在关联，但两者之间的因果关系仍不明确，本研究旨在对此进行探索。
我们基于公开的全基因组关联研究数据，利用两样本孟德尔随机化（MR）分析研究了mtDNA拷贝数与OSA之间的因果关系，并使用中介MR分析探索了免疫细胞在两者之间的中介作用。我们主要使用逆方差加权法估计因果效应，并基于MR-Egger截距法和 Cochr an's Q检验进行敏感性分析。
我们发现mtDNA拷贝数对OSA有显著的负向因果效应（优势比[OR][95%置信区间（CI）]=0.844[0.778-0.911]，p=0.03），而OSA对mtDNA拷贝数没有因果效应（OR[95%CI]=0.995[0.979-1.01]，p=0.791）。我们确定终末分化的CD4-CD8 T细胞绝对计数符合中介分析的要求（OR[95%CI]=0.989[0.985-0.993]，p=0.016，OR[95%CI]0.717[0.529-0.973]，p=0.033）。在此条件下，免疫细胞的中介效应大小为0.003，无论是使用自助法还是两步法，均认为没有中介效应（p>0.05）。
我们的研究表明，降低mtDNA拷贝数是OSA发生发展的一个危险因素，而非其结果。改善线粒体功能障碍可能有助于预防或治疗OSA。
