Epigenome-Wide Analysis of Differential DNA Methylation in Levodopa-Induced Dyskinesia in Parkinson’s Disease – Pilot Study

Introduction: Levodopa (L-DOPA) remains the gold-standard therapy for Parkinson’s disease (PD). However, chronic exposure commonly results in levodopa-induced dyskinesia (LiD) - a debilitating motor complication characterised by chorea, dystonia and athetosis. Rat studies suggest DNA methylation changes are associated with LiD. This study represents the first attempt to characterise the human LiD methylome. / Aim: This study investigated differential DNA methylation at LiD to identify potential epigenetic contributions to its development. / Methods: Illumina MethylationEPIC v1.0 array data and participant metadata from the Parkinson’s Progression Markers Initiative (PPMI) dataset were analysed. A genome-wide differentially methylated position (DMP) analysis was performed on paired samples from sixteen individuals at two time points: pre-LiD PD (MDS-UPDRS Part IV < 2) and LiD onset (MDS-UPDRS Part IV > 2). / Results: No CpG sites (DMPs) reached statistical significance at either FDR q