Rare GCH1 Variant Associated With Parkinson’s Disease Risk in East Asian Populations

Researchers investigated the Parkinson’s disease (PD) risk and clinical features associated with GCH1 p.Ser80Asn after identifying the variant through whole-genome sequencing in a Malaysian Chinese family with PD. They assessed its association with PD using multi-ancestry data from the Global Parkinson’s Genetics Program (GP2), comprising 22,372 cases and 8,826 controls, and a meta-analysis of East Asian cohorts comprising 4,712 cases and 38,733 controls.

The variant was present in 9 of 2,757 East Asian GP2 participants with PD (0.33%) and was not detected in other ancestries in the analyzed data. The East Asian meta-analysis found higher odds of PD among carriers (odds ratio 5.1; 95% CI 2.3–10.7; P=2.89×10⁻⁵). Carriers shared an approximately 330-kbp haplotype. Affected carriers had a mean age at onset of 56.3 ± 12.5 years; dystonia also occurred, whereas dementia was rare.

These findings identify a rare, East Asian–enriched genetic risk association rather than establish an individual carrier’s absolute probability of developing PD. The rarity of the variant and wide confidence interval limit precision. Only the abstract was available for assessment, and the reported findings do not establish clinical screening utility.