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Updated: May 7, 2025
Noninvasive, High-throughput Determination of Sleep Duration in Rodents
Published on: April 18, 2018
White Matter Imaging Phenotypes Mediate the Negative Causality of Mitochondrial DNA Copy Number on Sleep Apnea: A
Qiaohui Ying1,2,3,4, Mingwei Wang5, Zichen Zhao1,2,3,4
1Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
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, P = 3.20×10-4), whereas SA did not have a causal effect on mtDNA-CN (OR = 1.0056, 95% CI = 0.9954-1.0159, P = 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% (P = 0.0450), and fractional anisotropy in the right sagittal stratum, with a mediation proportion of 12.79% (P = 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.
Insights
Mitochondrial DNA copy number (mtDNA-CN) causally influences sleep apnea (SA), with brain white matter microstructure mediating this effect. This suggests mtDNA-CN may be a biomarker for SA and guide future therapies.
Area of Science:
- Genetics
- Neurology
- Sleep Medicine
Background:
- Sleep apnea (SA) involves breathing cessation during sleep, leading to hypoxemia and health issues.
- Mitochondrial DNA copy number (mtDNA-CN) in blood reflects mitochondrial function but its link to SA is unclear.
Purpose of the Study:
- To investigate the causal relationship between mtDNA-CN and SA.
- To identify potential mediating brain imaging phenotypes (BIPs) in this relationship.
Main Methods:
- Two-sample bidirectional Mendelian randomization (MR) analysis.
- Bayesian framework-based MR analysis and product of coefficients method for mediation analysis.
- Benjamini-Hochberg correction for multiple testing.
Main Results:
- Genetically predicted mtDNA-CN had a negative causal effect on SA (OR=0.859, P=3.20×10⁻⁴).
- SA did not show a causal effect on mtDNA-CN (OR=1.0056, P=0.2825).
- Two white matter microstructure features (right posterior thalamic radiation eigenvalue and right sagittal stratum fractional anisotropy) partially mediated the effect.
Conclusions:
- A causal link exists between mtDNA-CN and SA.
- Brain white matter microstructure phenotypes mediate this relationship, suggesting potential therapeutic targets.
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