Mendelian Randomization Analysis Identifies Causal Effects of Multi-Site Chronic Pain on Obstructive Sleep Apnea.

IF 3 2区医学 Q2 CLINICAL NEUROLOGY

Nature and Science of Sleep Pub Date : 2025-03-18 eCollection Date: 2025-01-01 DOI:10.2147/NSS.S487056

Zuxing Wang, Lili Chen, Ruishi Kang, Zhuowei Li, Jiangang Fan, Yi Peng, Yunqi He, Xiaolong Zhao

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Abstract

Background: Observational studies have suggested an association between obstructive sleep apnea (OSA) and chronic pain disorders, but causal evidence have not been confirmed.

Methods: Here we performed Mendelian randomization (MR) study to explore the potential causal association and mediating roles of modifiable factors between multi-site chronic pain (MCP) and OSA. Independent single nucleotide polymorphisms (SNPs) (N=26) from MCP GWAS (n=387,649) in the UK Biobank were used as instrumental variables to test associations with OSA from the FinnGen consortium, which encompassed 16,761 individuals with OSA cases and 201,194 individuals without OSA.

Results: MR analyses provide genetic evidence to predict MCP on the risk of OSA. Specifically, a per-site increase in multi-site chronic pain was linked to a 184% higher risk of OSA (OR_IVW = 1.84, 95% CI = 1.29-2.63, p = 7.24×10^-4). However, we also performed reverse association analyses and found no significant casual effect of OSA on MCP. MR estimates were in agreement regardless of the method used, such as MR-egger, weighted median and weighted mode, thereby demonstrating the accuracy of the causal associations. Through mediation analyses, we found that body mass index (BMI), waist circumference, and educational attainment explained a substantial proportion of the association between MCP and OSA (proportion mediated=21.13%; 26.57% and 9.66% respectively).

Conclusion: Our findings suggest that both pain management interventions, prevention of obesity and health education are likely to be effective strategies to reduce OSA risk in individuals with MCP.

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孟德尔随机分析确定多部位慢性疼痛对阻塞性睡眠呼吸暂停的因果影响。

背景：观察性研究表明阻塞性睡眠呼吸暂停（OSA）与慢性疼痛障碍之间存在关联，但因果证据尚未得到证实。方法：采用孟德尔随机化（Mendelian randomization， MR）研究，探讨多部位慢性疼痛（MCP）与OSA之间的潜在因果关系及可变因素的中介作用。来自英国生物银行MCP GWAS （N= 387,649）的独立单核苷酸多态性（SNPs）（N=26）被用作工具变量来测试FinnGen联盟与OSA的相关性，该联盟包括16,761例OSA患者和201,194例非OSA患者。结果：MR分析为预测MCP对OSA风险的影响提供了遗传证据。具体来说，多部位慢性疼痛的每个部位增加与OSA风险增加184%相关（ORIVW = 1.84, 95% CI = 1.29-2.63, p = 7.24×10-4）。然而，我们也进行了反向关联分析，发现OSA对MCP没有显著的随机影响。无论使用何种方法，如egger、加权中位数和加权模式，MR估计都是一致的，从而证明了因果关系的准确性。通过中介分析，我们发现身体质量指数（BMI）、腰围和受教育程度解释了MCP和OSA之间的很大一部分关联(中介比例=21.13%；26.57%和9.66%)。结论：我们的研究结果表明，疼痛管理干预、预防肥胖和健康教育可能是降低MCP患者OSA风险的有效策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.