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PURPOSE

Sleep apnea (SA), associated with absent neural output, is characterised by recurrent episodes of hypoxemia and repeated arousals during sleep, resulting in decreased sleep quality and various health complications. Mitochondrial DNA copy number (mtDNA-CN), an easily accessible biomarker in blood, reflects mitochondrial function. However, the causal relationship between mtDNA-CN and SA remains unclear. This study aimed to investigate the causality between mtDNA-CN and SA while identifying potential mediating brain imaging phenotypes (BIPs).

METHODS

Two-sample bidirectional Mendelian randomisation (MR) analysis was performed to estimate the causal relationship between mtDNA-CN and SA, with further validation using Bayesian framework-based MR analysis. A two-step approach was employed to evaluate causal relationships between BIPs, mtDNA-CN and SA, utilising the "product of coefficients" method to assess the mediating effects of BIPs. Multiple testing errors were corrected using the Benjamini-Hochberg method.

RESULTS

Genetically predicted mtDNA-CN had a negative causal effect on SA (OR = 0.859, 95% CI = 0.785-0.939, = 3.20×10), whereas SA did not have a causal effect on mtDNA-CN (OR = 1.0056, 95% CI = 0.9954-1.0159, = 0.2825). Among 3935 BIPs, two features related to white matter microstructure served as partial mediators: the second eigenvalue from diffusion MRI data analysed by tract-based spatial statistics in the right posterior thalamic radiation, with a mediation proportion of 11.37% ( = 0.0450), and fractional anisotropy in the right sagittal stratum, with a mediation proportion of 12.79% ( = 0.0323).

CONCLUSION

This study demonstrated a causal relationship between mtDNA-CN and SA, with specific brain white matter microstructure phenotypes potentially acting as mediators. These findings highlight the potential of mtDNA-CN as a biomarker for SA and underscore its relevance in guiding future therapeutic strategies targeting mitochondrial health and brain white matter microstructure.

PURPOSE

METHODS

RESULTS

CONCLUSION

目的

睡眠呼吸暂停（SA）与神经输出缺失相关，其特征为睡眠期间反复出现低氧血症发作和反复觉醒，导致睡眠质量下降及各种健康并发症。线粒体DNA拷贝数（mtDNA-CN）是血液中一种易于获取的生物标志物，反映线粒体功能。然而，mtDNA-CN与SA之间的因果关系仍不明确。本研究旨在探讨mtDNA-CN与SA之间的因果关系，同时确定潜在的中介脑成像表型（BIPs）。

方法

进行两样本双向孟德尔随机化（MR）分析以估计mtDNA-CN与SA之间的因果关系，并使用基于贝叶斯框架的MR分析进行进一步验证。采用两步法评估BIPs、mtDNA-CN和SA之间的因果关系，利用“系数乘积”方法评估BIPs的中介效应。使用Benjamini-Hochberg方法校正多重检验误差。

结果

基因预测的mtDNA-CN对SA有负向因果效应（OR = 0.859，95%CI = 0.785 - 0.939， = 3.20×10），而SA对mtDNA-CN没有因果效应（OR = 1.0056，95%CI = 0.9954 - 1.0159， = 0.2825）。在3935个BIPs中，两个与白质微观结构相关的特征作为部分中介：通过基于体素的空间统计学分析扩散MRI数据得出的右侧丘脑后辐射的第二特征值，中介比例为11.37%（ = 0.0450），以及右侧矢状层的分数各向异性，中介比例为12.79%（ = 0.0323）。