Psoriasis and progression of Parkinson's disease: a Mendelian randomization study

Background Epidemiological studies have suggested psoriasis was associated with an increased risk of Parkinson's disease (PD). However, whether psoriasis has an effect on PD progression is not explored yet. Objectives To evaluate the causal role of psoriasis in PD progression. Methods We conducted a two-sample Mendelian randomization analysis using summary statistics from genome-wide association study of psoriasis (N = 33 394), age at onset (N = 28 568) and progression (N = 4093) of PD. Results One standard deviation increase in genetically determined psoriasis risk was significantly associated with faster progression to dementia (OR = 1.07, 95% CI: 0.1.03-1.1, P = 4.71E-04). Meanwhile, higher psoriasis risk was nominally associated with faster progression of PD measured by time to Hoehn and Yahr stage 3 (OR = 1.05, 95% CI: 1.02-1.08, P = 1.53E-03) and depression (OR = 1.06, 95% CI: 1.02-1.11, P = 1.77E-03) of PD. The results were robust under all sensitivity analyses. Conclusions These results suggested psoriasis accelerated overall progression of PD, and increased risk of dementia and depression of PD. A deeper understanding of neuroinflammation and immune response is likely to elucidate the potential pathogenesis of PD progression and identify novel therapeutic targets.