Bidirectional Mendelian randomization analysis of inflammatory factors and sleep related traits

Abstract

Backgrounds: Observational research has shown significant associations between inflammatory factors and sleep. Experimental studies suggested acute increase in the levels of inflammatory markers following sleep deprivation and sleep restriction. However, the causal association between inflammatory factors and sleep remains unclear in chronic and natural settings. Objectives: This study aimed to investigate the causal association of inflammatory factors with chronotype, daytime napping, daytime sleepiness, insomnia symptoms, and sleep duration. Methods: Two-sample bidirectional Mendelian randomization (MR) analysis was employed to investigate the causal associations between 91 inflammatory factors and 7 sleep-related traits. Summary-level data of inflammatory factors were derived from the EBI GWAS Catalog (n = 14,824); sleep-related traits were obtained from UK Biobank. We calculated effect estimates using the inverse-variance weighted (IVW), weighted median, and MR-Egger methods. Heterogeneity and pleiotropy were detected and measured by the MR pleiotropy residual sum and outlier, Cochran's Q statistics, and MR-Egger regression. Results: Significant bidirectional causal associations were observed. The most crucial findings included the causal effects of CD40 (OR = 1.02, 95 % CI: 1.01-1.03), ST1A1 (OR = 0.97, 95 % CI: 0.96-0.99), uPA (OR = 1.03, 95 % CI: 1.01-1.04) on chronotype, and FGF-21 (OR = 1.02, 95 % CI: 1.01-1.03), hGDNF (OR = 1.01, 95 % CI: 1.00-1.02), TNFB (OR = 0.99, 95 % CI: 0.98-1.00), TNFSF14 (OR = 1.01, 95 % CI: 1.00-1.02) on napping. Overall, 30 inflammatory factors were found to causally affect sleep traits, and 20 reciprocal effects were observed. Conclusion: Our study suggested a bidirectional causal association between inflammatory factors and sleep-related traits, such as the roles of CD40, ST1A1, and uPA in regulating chronotype, and FGF-21, hGDNF, and TNFB in influencing daytime napping.