DoesCOMTPlay 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
To investigate the relationship betweenCOMTgenetic variants and PD risk across diverse ancestries.
Methods
We analyzedCOMTvariants in 2,251 PD patients and 2,835 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
Utilizing the largest case-control datasets to date, no significant enrichment ofCOMTrisk 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 LID onset were observed.
Conclusions
These findings emphasize the need for larger, diverse cohorts to confirm the role ofCOMTin PD development and progression.
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