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 = 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).

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.