Circadian rhythm disruption is increasingly recognized as a driver of systemic inflammation, but how lifestyle-related circadian imbalance and genetic predisposition combine to affect psoriasis risk was unclear. Researchers followed 260,118 UK Biobank participants for a mean of 16.49 years; 2,519 developed psoriasis. They built a circadian imbalance index (CII) from five factors—chronotype, sleep timing, neuroticism, caffeine intake, and vitamin D levels—with higher scores meaning greater imbalance. Genetic risk was measured with a polygenic risk score (PRS).

After full adjustment, each one-point increase in CII was linked to a 10% higher risk of psoriasis (HR 1.10), and the high CII group had a 37% higher risk than the low CII group (HR 1.37), with a dose-response relationship. The highest risk was in people with both high CII and high genetic risk: 2.63 times that of those with low CII and low genetic risk. A positive additive interaction was found, meaning the combined effect was greater than the sum of separate effects (RERI 0.69 and AP 26% for high CII/high genetic risk; RERI 0.28 and AP 19% for middle CII/moderate genetic risk). Mediation analysis showed that inflammatory, liver, kidney, and glucose/lipid metabolic blood biomarkers partly mediated the association, with alkaline phosphatase (ALP) having the largest mediation proportion (2.61%) and monocyte count (MONO) the smallest (0.07%).

The authors conclude that circadian imbalance is an independent risk factor for psoriasis, especially among people with high genetic susceptibility, and that improving circadian-related behaviors may be an important preventive strategy. Because the study is observational, it cannot prove causality. Limitations include single-time measurement of circadian imbalance, healthy volunteer bias, limited ability to distinguish psoriasis severity from ICD codes, residual confounding, mainly European ancestry, and lack of objective circadian validation.

The work titled “Circadian Imbalance, Genetic Susceptibility, and Risk of Psoriasis” was published on Skin (published on September 10, 2026).
DOI:10.2738/SKIN.2026.0041