Epigenome-Wide Analysis of Differential DNA Methylation at Levodopa-Induced Dyskinesia onset in Parkinson's Disease

Poster Abstract: Rayian Higzi, Methylation Arrays Application Specialist, UCL Genomics

Abstract

Background: 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. Preclinical studies implicate DNA methylation changes in LiD pathogenesis, yet the human LiD methylome remains uncharacterised. This study investigated differential DNA methylation at LiD onset to identify potential epigenetic contributions to its development. 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. No CpG sites (DMPs) reached statistical significance at either FDR q<0.05 or q<0.20 thresholds. Findings may reflect limited cohort size or subtle methylomic effects, highlighting the need for larger, longitudinal studies to clarify LiD-associated DNA methylation changes in PD.