Sleep patterns and the risk of psoriatic disease: genetic predisposition and metabonomics.

BACKGROUND

The longitudinal impact of comprehensive sleep patterns on incident psoriatic disease (PsD) and the potential mediating effects are 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 participants without PsD registered in UK Biobank. Cox proportional hazard models were used to examine the association between sleep patterns, genetic risk of PsD and the overall 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 used to identify specific metabolites as potential mediators of PsD.

RESULTS

During a mean follow-up of 14.7 years, 4001 new cases of PsD were identified. Compared with those with high PRS and low sleep scores, participants with low PRS and high sleep scores had the lowest risk of PsD [hazard ratio 0.35, 95% confidence interval (CI) 0.28-0.43]. Although no significant interaction between PRS and sleep score was initially detected (P = 0.08), subsequent analyses using a median-dichotomized PRS revealed multiplicative (P = 0.003) and additive interactions (RERI 0.36, 95% CI 0.17-0.55; P < 0.001). Mediation analyses identified glycoprotein acetylation, the ratio of polyunsaturated fatty acids to monounsaturated fatty acids 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 a high genetic predisposition to PsD. This association is partially mediated by inflammatory and metabolic biomarkers, highlighting sleep optimization as a modifiable lifestyle factor for mitigating PsD risk.