Does <scp> <i>COMT</i> </scp> Play a Role in Parkinson's Disease Susceptibility across Diverse Ancestral Populations?

Abstract

BACKGROUND: The catechol-O-methyltransferase (COMT) gene is involved in brain catecholamine metabolism, but its association with Parkinson's disease (PD) risk remains unclear. OBJECTIVE: Our aim was to investigate the relationship between COMT genetic variants and PD risk across diverse ancestries. METHODS: We analyzed COMT variants in 2251 PD patients and 2835 controls of European descent using whole-genome sequencing from the Accelerating Medicines Partnership-Parkinson Disease (AMP-PD), along with 20,427 PD patients and 11,837 controls from 10 ancestries using genotyping data from the Global Parkinson's Genetics Program (GP2). RESULTS: Using the largest case-control datasets to date, no significant enrichment of COMT risk alleles in PD patients was observed across any ancestry group after correcting for multiple testing. Among Europeans, no correlations with cognitive decline, motor function, motor complications, or time to levodopa-induced dyskinesia onset were observed. CONCLUSIONS: This study highlights the need for increased representation of diverse ancestries to better understand the role of COMT variants in PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.