Files and links (1)
Open Access CC BY V4.0
Preprint
GCH1 p.Ser80Asn Confers Risk for Parkinson's Disease in East Asian Populations
medRxiv
Cold Spring Harbor Laboratory Press
2026
PMID: 42396327
Abstract
Introduction
GCH1 has been implicated in Parkinson’s disease (PD), but its risks variants and associations are not well defined.
Objectives
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). 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%CI:2.3–10.7; p=2.89×10−5). Affected carriers (mean age at onset:56.3±12.5 years) had additional occurrence of dystonia, while dementia was rare.
Conclusions
The GCH1 p.Ser80Asn variant is a rare, EAS-enriched risk variant for PD.
Details
- Title
- GCH1 p.Ser80Asn Confers Risk for Parkinson's Disease in East Asian Populations
- Authors/Creators
- Yi Wen Tay - University of MalayaAndrew Leslie Lee - University of MalayaJie Ping Schee - University of MalayaChin Hsien Lin - National Taiwan University HospitalEng King Tan - National University of SingaporeJung Hwan Shin - Seoul National University HospitalPin-Shiuan Chen - National Taiwan University HospitalSung-Pin FanCheng-Hsuan LiEbonne Ng Yu LinHan Joon KimBeomseok Jeon - Seoul National University HospitalSulev Koks - Murdoch UniversityKin Ying Mok - Hong Kong University of Science and TechnologyYi Ting Lim - University of MalayaMohd Salahuddin KamaruddinTzi Shin Toh - University of MalayaHans Xing Ding - University of MalayaAnis Nadhirah Khairul AnuarNorlisah RamliIgnacio Juan Keller Sarmiento - Northwestern UniversityMaria Teresa Periñan - Hospital Universitario Virgen del RocíoZih-Hua FangLara M Lange - University of LübeckKishore R Kumar - Garvan Institute of Medical ResearchSoraya Bardien - South African Medical Research CouncilJoanne Trinh - University of LübeckEnza Maria Valente - University of PaviaPeter Heutink - University of LübeckKatja Lohmann - University of LübeckChristine Klein - University of LübeckNiccolò E Mencacci - Northwestern UniversityShen-Yang LimAzlina Ahmad-AnnuarAi Huey Tan - National University of SingaporeSG10K_Health Consortium
- Publication Details
- medRxiv
- Publisher
- Cold Spring Harbor Laboratory Press
- Identifiers
- 991005902122407891
- Copyright
- The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
- Murdoch Affiliation
- Personalised Medicine Centre
- Language
- English
- Resource Type
- Preprint
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: SDGs in the Output
Metrics
1 Record Views