Sleep and degenerative skeletal disorders: an Observational and Mendelian randomization study

Abstract Objectives : Skeletal degeneration is influenced by genetics, environment and lifestyle, but the role of sleep in its development remains uncertain. This study investigates the association between sleep and the risk of degenerative skeletal disorders, aiming to identify the impact of specific sleep characteristics on skeletal disorder phenotypes. Methods : The observational study utilized health data from 387,822 UK Biobank participants. Cox proportional risk regression estimated the association between sleep and degenerative skeletal disorders. Two-sample MR analyses validated the bidirectional causal relationships based on genetic associations summary data of sleep characteristics from UK Biobank and skeletal disorders from FinnGen as well as meta GWAS, using inverse-variance weighted (IVW), MR-PRESSO, weighed median and MR-Egger. Results: In observational study, 37 pairs of exposure-disease risk associations were identified between six sleep characteristics and eight degenerative skeletal phenotypes. The risk of degenerative skeletal disorders was increased with unhealthy sleep characteristics. MR analysis confirmed four robust causality associations: short sleep duration with overall OA (OR=2.88, 95%CI: 1.63-5.07), knee OA (OR=2.50, 95%CI: 1.33-4.68), and LDD (OR=2.97, 95%CI: 1.63-5.41), and long sleep duration with LDD (OR=0.13, 95%CI: 0.03-0.53). Four positive associations were considered potentially causal, including insomnia with LDD and spondylosis, early chronotype with overall OA, and short sleep duration with CDD. Conclusions and Relevance: Large prospective observational and MR studies suggest a causal effect of sleep on spine and peripheral joint degeneration, emphasizing the value of sleep management in ameliorating joint degeneration.