MC1R loss-of-function is associated with accelerated Parkinson’s disease motor decline

Background: loss-of-function variants, especially those previously associated with an increased risk of PD, are associated with PD progression and phenoconversion. Methods: ) using time-to-event survival analysis. Results: loss-of-function variants exhibited a 3.81-fold increased risk of phenoconversion compared to noncarriers (p=0.059). Interpretation: loss-of-function variants are associated with accelerated PD motor decline in the PPMI cohort. Together with previous biological findings from our group and others, these results highlight the potential role of MC1R in PD prognosis, warranting further validation and investigation into whether MC1R-targeted interventions may modify PD progression.