Proteome-Wide Association Study for Finding Druggable Targets in Progression and Onset of Parkinson's Disease.

Résumé

OBJECTIVE: To identify and validate causal protein targets that may serve as potential therapeutic interventions for both the onset and progression of Parkinson's disease (PD) through integrative proteomic and genetic analyses.METHOD: We utilized large-scale plasma and brain protein quantitative trait loci (pQTL) datasets from the deCODE Health study and the Religious Orders Study/Rush Memory and Aging Project (ROS/MAP), respectively. Proteome-wide association studies (PWAS) were conducted using the OTTERS framework for plasma proteins and the FUSION tool for brain proteins, examining associations with PD onset and three progression phenotypes: composite, motor, and cognitive. Significant protein associations (FDR-corrected p