Wang Zuxing, Chen Lili, Kang Ruishi, Li Zhuowei, Fan Jiangang, Peng Yi, He Yunqi, Zhao Xiaolong
Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, 610072, People's Republic of China.
Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
Nat Sci Sleep. 2025 Mar 18;17:463-473. doi: 10.2147/NSS.S487056. eCollection 2025.
Observational studies have suggested an association between obstructive sleep apnea (OSA) and chronic pain disorders, but causal evidence have not been confirmed.
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.
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 = 1.84, 95% CI = 1.29-2.63, p = 7.24×10). 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).
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.
观察性研究表明阻塞性睡眠呼吸暂停（OSA）与慢性疼痛疾病之间存在关联，但因果证据尚未得到证实。
在此，我们进行了孟德尔随机化（MR）研究，以探讨多部位慢性疼痛（MCP）和OSA之间潜在的因果关联以及可改变因素的中介作用。来自英国生物银行中MCP全基因组关联研究（n = 387,649）的独立单核苷酸多态性（SNP）（N = 26）被用作工具变量，以检验与芬兰基因联盟中OSA的关联，该联盟包括16,761例OSA患者和201,194例无OSA的个体。
MR分析提供了遗传证据来预测MCP对OSA风险的影响。具体而言，多部位慢性疼痛每增加一个部位，与OSA风险高出184%相关（优势比 = 1.84，95%置信区间 = 1.29 - 2.63，p = 7.24×10）。然而，我们也进行了反向关联分析，未发现OSA对MCP有显著的因果效应。无论使用何种方法，如MR-egger、加权中位数和加权模式，MR估计结果均一致，从而证明了因果关联的准确性。通过中介分析，我们发现体重指数（BMI）、腰围和受教育程度在很大程度上解释了MCP与OSA之间的关联（中介比例分别为21.13%、26.57%和9.66%）。
我们的研究结果表明，疼痛管理干预、预防肥胖和健康教育都可能是降低MCP个体OSA风险的有效策略。
