Sleep patterns and the Risk of Psoriatic disease: Insights from Genetic Predisposition and Metabonomics

Background The longitudinal impact of comprehensive sleep patterns on incident psoriatic disease (PsD) and the potential mediating effect remain unclear. Objectives To investigate the associations of sleep patterns with PsD risk, alongside the role of genetic predisposition and the potential mediating effects of serum metabolites. Methods This prospective cohort study included 399,912 PsD-free UK Biobank participants. Cox proportional hazard models were used to examine the association between sleep patterns, genetic risk of PsD and the risk of PsD. Cross-product interaction terms between polygenic risk score (PRS) categories and sleep patterns were incorporated into the fully adjusted models, and the relative excess risk due to interaction (RERI) was calculated to examine additive interaction. Mediation analyses were employed to identify specific metabolites as potential mediators. Results During an average follow-up of 14.7 years, 4,001 new cases of PsD were identified. Compared with those with high PRS and low sleep scores, participants with low PRS and high sleep scores were associated with the lowest risk of PsD (hazard ratio, 0.34; 95% confidence interval (CI): 0.28–0.43). Although no significant interaction between PRS and sleep score was initially detected (P = 0.075), subsequent analyses using a median-dichotomized PRS revealed both multiplicative (P = 0.003) and additive interactions (RERI = 0.36, 95% CI: 0.17–0.55; p < 0.001). Mediation analyses identified GlycA, PUFA/MUFA ratio, and alkaline phosphatase as partial mediators of the sleep-PsD association. Conclusions Unfavourable sleep patterns significantly increase the risk of PsD, especially in people with high genetic predisposition. This association is partially mediated by inflammatory and metabolic biomarkers, highlighting sleep optimization as a modifiable lifestyle factor for mitigating PsD risk.