Association Between Sleep Apnea Syndrome and Osteoarthritis: Insights from Bidirectional Mendelian Randomization and Bioinformatics Analysis

IF 3 2区 医学 Q2 CLINICAL NEUROLOGY
Lian Weng, Xiongjunjie Luo, Yuxi Luo, Qian Zhang, Kaitao Yao, Junjie Tan, Yiran Yin
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Abstract

Background: Sleep apnea syndrome(SAS) and osteoarthritis (OA) are two prevalent diseases that often coexist, but the causal relationship between them remains unclear. In light of this, our team utilizes Mendelian Randomization and bioinformatics analysis methods to investigate the potential association between the two diseases.
Methods: In this study, we utilized GWAS data pertaining to SAS and OA to assess the causal relationship between the two diseases through Mendelian randomization (MR) analysis. We then employed transcriptomic data to perform differential gene identification, WGCNA, shared gene determination, functional enrichment analysis, and colocalization analysis, all designed to further elucidate the mechanisms underlying the association between the two diseases. In the end, we utilized Mendelian randomization (MR) analysis again to delve deeper into the relationship between the two diseases and immune cells.
Results: Our research findings indicate that SAS is a risk factor for OA (p = 0.000004), knee OA (p = 0.0000001) and hip OA(p = 0.001). Furthermore, OA (p = 0.000195), knee OA (p = 0.001) are significant risk factors for SAS. However, there is no clear evidence that hip OA (p = 0.892) is a risk factor for SAS. Interestingly, the genes shared between OA and SAS are significantly enriched in leukocyte migration, leukocyte chemotaxis. Moreover, colocalization analysis suggests that the genes JUNB, COL8A1, FOSB, and IER2 may be key genes associated with both diseases. Furthermore, 57 immune cell phenotypes are associated with SAS, 95 with OA, and 6 shared between both diseases.
Conclusion: This research confirmed the bidirectional causal relationship between SAS and OA. Notably, the 4 genes (JUNB, COL8A1, FOSB, IER2) and 6 immune phenotypes are crucial for both diseases, these provide hopeful targets for future interventions against these two diseases.

睡眠呼吸暂停综合征与骨关节炎之间的关系:双向孟德尔随机化和生物信息学分析的启示
背景:睡眠呼吸暂停综合征(SAS)和骨关节炎(OA)是两种经常并存的常见疾病,但它们之间的因果关系仍不清楚。有鉴于此,我们的团队利用孟德尔随机化和生物信息学分析方法研究这两种疾病之间的潜在关联:在这项研究中,我们利用有关 SAS 和 OA 的 GWAS 数据,通过孟德尔随机化(MR)分析评估这两种疾病之间的因果关系。然后,我们利用转录组数据进行了差异基因鉴定、WGCNA、共享基因确定、功能富集分析和共定位分析,旨在进一步阐明这两种疾病之间的关联机制。最后,我们再次利用孟德尔随机分析法(MR)深入研究了这两种疾病与免疫细胞之间的关系:我们的研究结果表明,SAS 是 OA(p = 0.000004)、膝关节 OA(p = 0.0000001)和髋关节 OA(p = 0.001)的危险因素。此外,OA(p = 0.000195)、膝关节 OA(p = 0.001)是 SAS 的重要风险因素。然而,没有明确证据表明髋关节 OA(p = 0.892)是 SAS 的风险因素。有趣的是,OA 和 SAS 的共有基因在白细胞迁移、白细胞趋化方面明显富集。此外,共定位分析表明,JUNB、COL8A1、FOSB 和 IER2 基因可能是与这两种疾病相关的关键基因。此外,57 种免疫细胞表型与 SAS 相关,95 种与 OA 相关,6 种与两种疾病共有:结论:这项研究证实了 SAS 和 OA 之间的双向因果关系。值得注意的是,4个基因(JUNB、COL8A1、FOSB、IER2)和6种免疫表型对这两种疾病都至关重要,这为未来干预这两种疾病提供了希望的靶点。
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来源期刊
Nature and Science of Sleep
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.
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