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Published on: June 18, 2018
GCH1 p.Ser80Asn Confers Risk for Parkinson's Disease in East Asian Populations
Yi Wen Tay1,2, Andrew Leslie Lee2, Jie Ping Schee2
1Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Introduction:
GCH1 has been implicated in Parkinson's disease (PD), but its risks variants and associations are not well defined.
Objectives:
Our goal was to investigate the clinical relevance and PD risk associated with the GCH1 p.Ser80Asn variant.
Methods:
We first identified a segregating GCH1 p.Ser80Asn variant in a Malaysian Chinese PD family via whole genome sequencing (WGS). We assessed its risk association using multi-ancestry WGS data from the Global Parkinson's Genetics Program (GP2) (n = 22,372PD vs. n = 8,826Controls) and meta-analysis of East Asian (EAS) cohorts (n = 4,712PD vs. 38,733Controls). Haplotype analyses were performed and clinico-demographic details of affected variant carriers were collated.
Results:
The GCH1 p.Ser80Asn variant was enriched in GP2 EAS PD populations (n = 9/2,757; 0.33%), but not detected in other ancestries. Meta-analysis revealed increased PD risk in EAS populations (odds ratio = 5.1; 95% confidence intervals [CI] = 2.3-10.7; P = 2.89 × 10-5). A shared haplotype (~330 kbp) was identified among variant carriers. Affected carriers (mean age at onset: 56.3 ± 12.5 years) had additional occurrence of dystonia, whereas dementia was rare.
Conclusions:
The GCH1 p.Ser80Asn variant is a rare, EAS-enriched risk variant for PD. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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