Associations Between Obstructive Sleep Apnea and Metabolic Dysfunction-Associated Fatty Liver Disease: Insights from Comprehensive Mendelian Randomization and Gene Expression Analysis.

IF 3.4 2区医学 Q2 CLINICAL NEUROLOGY

Nature and Science of Sleep Pub Date : 2025-07-08 eCollection Date: 2025-01-01 DOI:10.2147/NSS.S511115

Tianyu Ma, Chunyan Liao, Wenhui Chen, Jia Feng

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引用次数: 0

Abstract

Background: Obstructive sleep apnea (OSA) is linked to metabolic dysfunction-associated fatty liver disease (MAFLD), yet their exact causality and underlying mechanisms remain inconclusive. We aimed to investigate their causal associations and shared biomarkers using Mendelian randomization (MR) and bioinformatics approaches.

Methods: We used OSA-related and MAFLD-related GWAS data to explore their causal relationship and the role of body mass index (BMI) through two-sample and network MR analysis. Gene expression profiles were analyzed to identify intersection genes through differential expression analysis and weighted gene co-expression network analysis (WGCNA). Functional enrichment (GO and KEGG), protein-protein interaction (PPI) networks, and immune cell infiltration analyses (ssGSEA) were performed on the intersecting genes. We then conducted MR analysis to assess the relationship between immune cells and both diseases. Inverse variance weighting (IVW) served as the primary MR method, supplemented by MR-Egger regression, weighted median, and weighted mode.

Results: MR analysis revealed that OSA increased the risk of MAFLD [odds ratio (OR)=1.40, 95% CI 1.14-1.73, p= 0.002], with OSA potentially mediating the effect of BMI on MAFLD, accounting for 62.3% of the mediation. Bioinformatics identified 42 intersection genes. Four hub genes (FOS, EGR1, NR4A1, JUN) were ultimately obtained by PPI network, which were strongly linked to immune cell infiltration. Additionally, three immune cell phenotypes (CD4RA on TD CD4+, HLA DR on CD14+ CD16-monocytes, and HLA DR on CD14+ monocytes) were found to be associated with both OSA and MAFLD.

Conclusion: OSA may causally influence MAFLD and mediate the effect of BMI on MAFLD. Four key genes and three immune cell phenotypes play crucial roles in the shared pathogenesis of both diseases.

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阻塞性睡眠呼吸暂停和代谢功能障碍相关脂肪肝之间的关联：来自孟德尔随机化和基因表达分析的见解

背景：阻塞性睡眠呼吸暂停（OSA）与代谢功能障碍相关的脂肪性肝病（MAFLD）有关，但其确切的因果关系和潜在机制尚不明确。我们的目的是利用孟德尔随机化（MR）和生物信息学方法调查它们的因果关系和共享的生物标志物。方法：采用双样本和网络MR分析方法，利用osa相关和mafld相关的GWAS数据，探讨两者的因果关系以及体重指数（BMI）在其中的作用。通过差异表达分析和加权基因共表达网络分析（WGCNA）分析基因表达谱，鉴定交叉基因。对交叉基因进行功能富集（GO和KEGG）、蛋白相互作用（PPI）网络和免疫细胞浸润分析（ssGSEA）。然后，我们进行了核磁共振分析，以评估免疫细胞与这两种疾病之间的关系。方差逆加权（IVW）为主要MR方法，MR- egger回归、加权中位数和加权模式为辅助MR方法。结果：MR分析显示，OSA增加了MAFLD的风险[比值比(OR)=1.40, 95% CI 1.14-1.73, p= 0.002]， OSA可能介导BMI对MAFLD的影响，占介导作用的62.3%。生物信息学鉴定出42个交叉基因。通过PPI网络最终获得与免疫细胞浸润密切相关的4个枢纽基因（FOS、EGR1、NR4A1、JUN）。此外，三种免疫细胞表型（CD4RA在TD CD4+上，HLA DR在CD14+ cd16单核细胞上，HLA DR在CD14+单核细胞上）被发现与OSA和MAFLD相关。结论：OSA可能与mald有因果关系，并介导BMI对mald的影响。四种关键基因和三种免疫细胞表型在两种疾病的共同发病机制中起着至关重要的作用。

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来源期刊

Nature and Science of Sleep Neuroscience-Behavioral Neuroscience

CiteScore

5.70

自引率

5.90%

发文量

245

审稿时长

16 weeks

期刊介绍： Nature and Science of Sleep is an international, peer-reviewed, open access journal covering all aspects of sleep science and sleep medicine, including the neurophysiology and functions of sleep, the genetics of sleep, sleep and society, biological rhythms, dreaming, sleep disorders and therapy, and strategies to optimize healthy sleep. Specific topics covered in the journal include: The functions of sleep in humans and other animals Physiological and neurophysiological changes with sleep The genetics of sleep and sleep differences The neurotransmitters, receptors and pathways involved in controlling both sleep and wakefulness Behavioral and pharmacological interventions aimed at improving sleep, and improving wakefulness Sleep changes with development and with age Sleep and reproduction (e.g., changes across the menstrual cycle, with pregnancy and menopause) The science and nature of dreams Sleep disorders Impact of sleep and sleep disorders on health, daytime function and quality of life Sleep problems secondary to clinical disorders Interaction of society with sleep (e.g., consequences of shift work, occupational health, public health) The microbiome and sleep Chronotherapy Impact of circadian rhythms on sleep, physiology, cognition and health Mechanisms controlling circadian rhythms, centrally and peripherally Impact of circadian rhythm disruptions (including night shift work, jet lag and social jet lag) on sleep, physiology, cognition and health Behavioral and pharmacological interventions aimed at reducing adverse effects of circadian-related sleep disruption Assessment of technologies and biomarkers for measuring sleep and/or circadian rhythms Epigenetic markers of sleep or circadian disruption.