GCH1 p.Ser80Asn Confers Risk for Parkinson's Disease in East Asian Populations.

Authors

Yi Wen Tay, Andrew Leslie Lee, Jie Ping Schee, Chin-Hsien Lin, Eng King Tan, Jung Hwan Shin, Pin-Shiuan Chen, Sung-Pin Fan, Cheng-Hsuan Li, Ebonne Yu Lin Ng, Han Joon Kim, Beomseok Jeon, Sulev Koks, Huyen Thi Thanh Vu, Kin Ying Mok, Yi Ting Lim, Mohd Salahuddin Kamaruddin, Tzi Shin Toh, Hans Xing Ding, Anis Nadhirah Khairul Anuar, Norlisah Ramli, Ignacio J Keller Sarmiento, Maria Teresa Periñan, Zih-Hua Fang, Lara M Lange, Kishore R Kumar, Soraya Bardien, Joanne Trinh, Enza Maria Valente, SG10K_Health Consortium, the Global Parkinson's Genetics Program (GP2), Peter Heutink, Katja Lohmann, Christine Klein, Niccolò E Mencacci, Shen-Yang Lim, Azlina Ahmad-Annuar, Ai Huey Tan

Published in

Movement disorders : official journal of the Movement Disorder Society. Oct 14, 2026. Epub Oct 14, 2026.

Abstract

GCH1 has been implicated in Parkinson's disease (PD), but its risks variants and associations are not well defined.
Our goal was to investigate the clinical relevance and PD risk associated with the GCH1 p.Ser80Asn variant.
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 = 22,372_PD vs. n = 8,826_Controls) and meta-analysis of East Asian (EAS) cohorts (n = 4,712_PD vs. 38,733_Controls). Haplotype analyses were performed and clinico-demographic details of affected variant carriers were collated.
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.
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.

PMID:
42876073
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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