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

Zuxing Wang1, Lili Chen1, Ruishi Kang2

  • 1Sichuan 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.

Nature and Science of Sleep
|March 24, 2025
PubMed
Abstract

Insights

Multi-site chronic pain (MCP) significantly increases the risk of obstructive sleep apnea (OSA), but OSA does not cause MCP. Interventions targeting pain, obesity, and education may reduce OSA risk in individuals with MCP.

Area of Science:

  • Genetics
  • Sleep Medicine
  • Pain Medicine

Background:

  • Observational studies suggest a link between obstructive sleep apnea (OSA) and chronic pain.
  • Causal evidence for this association remains unconfirmed.

Purpose of the Study:

  • To investigate the potential causal relationship between multi-site chronic pain (MCP) and OSA using Mendelian randomization (MR).
  • To explore the mediating roles of modifiable factors in the MCP-OSA association.

Main Methods:

  • Utilized 26 independent single nucleotide polymorphisms (SNPs) from a large MCP Genome-Wide Association Study (GWAS) as instrumental variables.
  • Tested associations with OSA using data from the FinnGen consortium (16,761 OSA cases, 201,194 controls).
  • Performed MR analyses, including MR-Egger and weighted median methods, and mediation analyses.

Main Results:

  • Genetic evidence supports MCP as a predictor of OSA risk; a per-site increase in MCP was associated with a 184% higher risk of OSA (ORIVW = 1.84).
  • Reverse association analyses found no significant causal effect of OSA on MCP.
  • Body mass index (BMI), waist circumference, and educational attainment significantly mediated the association between MCP and OSA.

Conclusions:

  • MCP is a likely causal risk factor for OSA.
  • Interventions for pain management, obesity prevention (BMI, waist circumference), and health education may reduce OSA risk in individuals with MCP.
Keywords:
Mendelian randomizationcausal effectmediation effectmulti-site chronic painobstructive sleep apnea

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