GCH1 genetic variation as a prognostic factor in Parkinson’s disease across populations
Rattachement africain : kr, gb, es, us, de, ca, cz, ru, il, tw, sg, cn, fr, Tunisie, my, gr, au, pe, it, lu. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Abstract Background Pathogenic variants in GCH1 have been associated with Parkinson’s disease (PD), but the clinical phenotype and longitudinal disease course of GCH1 -associated PD remain incompletely characterized. Objectives To characterize the genetic spectrum, clinical phenotype, and longitudinal progression of GCH1 -associated PD across multiple populations. Methods Whole-genome sequencing (WGS) and clinical exome sequencing (CES) data from the Global Parkinson’s Genetics Program (GP2) were analyzed together with unpublished and published GCH1-associated PD patients. Variant pathogenicity was classified according to ACMG criteria. Demographic, clinical, and longitudinal features were compared between GCH1 P/LP variant carriers and non-carrier PD patients; individuals with known pathogenic variants in PD-associated genes were excluded from both groups. Results In the GP2 cohort (PD, n=22,825; controls, n=4,453), 16 pathogenic or likely pathogenic (P/LP) GCH1 variants were identified in 58 individuals, including 54 PD patients, one control, and three individuals with other neurodegenerative phenotypes (two with progressive supranuclear palsy and one with dementia with Lewy bodies). In the pooled-ancestry WGS analysis, GCH1 P/LP variants were enriched in PD patients versus controls (0.267% vs 0.023%; OR=11.854; 95% CI=1.620-86.699; p =0.0006). Variant frequencies in PD patients ranged from 0.121% to 0.714% across ancestries. In the CES cohort, P/LP variants were identified in 0.201% of PD patients. After integrating GP2 with additional unpublished and published datasets, 119 GCH1-associated PD patients were analyzed. Compared with non-carriers, GCH1 P/LP variant carriers had earlier disease onset (53.7 ± 14.8 vs 59.2 ± 11.7 years; p =8.99×10 -5 ), lower levodopa equivalent daily dose requirements (467.5 ± 331.7 vs 680.3 ± 466.39mg/day; p =4.21×10 -8 ), and more frequent family history of PD (47.6% vs 19.9%; p =1.09×10 -8 ). Adjusted Cox models showed significant delayed progression to motor fluctuations (HR=0.32, 95% CI=0.16-0.62) and levodopa-induced dyskinesias (HR=0.51, 95% CI=0.30-0.87). Conclusion GCH1 pathogenic variants were associated with a clinically distinct phenotype characterized by earlier disease onset and slower progression of motor complications. These findings suggest that GCH1 genetic variants may serve as genetic biomarkers for patient stratification and prognosis in PD.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- <i>GCH1</i> genetic variation as a prognostic factor in Parkinson’s disease across populations
- Date Crossref
- 14/08/2026
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Seoul National University Hospital Department of Neurology pays non établi dans la noticeÉtablissement de santé
-
Queen Mary University of London Wolfson Institute of Population Health pays non établi dans la noticeUniversité ou école supérieure
-
Hospital Universitario Virgen del Rocío pays non établi dans la noticeÉtablissement de santé
-
National Institutes of Health pays non établi dans la noticeOrganisme public
-
National Institute on Aging pays non établi dans la noticeStructure de recherche
-
University of Lübeck Institute of Neurogenetics pays non établi dans la noticeUniversité ou école supérieure
-
Baylor College of Medicine Department of Molecular and Human Genetics pays non établi dans la noticeUniversité ou école supérieure
-
McGill University Department of Neurology and Neurosurgery pays non établi dans la noticeUniversité ou école supérieure
-
Charles University Department of Neurology and Centre of Clinical Neuroscience pays non établi dans la noticeUniversité ou école supérieure
-
Institute of the Human Brain pays non établi dans la noticeStructure de recherche
-
Tel Aviv Sourasky Medical Center pays non établi dans la noticeÉtablissement de santé
-
National Taiwan University Hospital Department of Neurology pays non établi dans la noticeÉtablissement de santé
Department of Neurology — Seoul National University Hospital, Wolfson Institute of Population Health — Queen Mary University of London et Hospital Universitario Virgen del Rocío, avec 9 autres affiliations. Pays d’affiliation : Tunisie.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.