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

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.