Polygenic Parkinson's Disease Genetic Risk Score as Risk Modifier of Parkinsonism in Gaucher Disease.
GBA1
Gaucher
Parkinson's
genetics
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
revised:
05
12
2022
received:
21
09
2022
accepted:
03
01
2023
pmc-release:
01
05
2024
medline:
13
6
2023
pubmed:
4
3
2023
entrez:
3
3
2023
Statut:
ppublish
Résumé
Biallelic pathogenic variants in GBA1 are the cause of Gaucher disease (GD) type 1 (GD1), a lysosomal storage disorder resulting from deficient glucocerebrosidase. Heterozygous GBA1 variants are also a common genetic risk factor for Parkinson's disease (PD). GD manifests with considerable clinical heterogeneity and is also associated with an increased risk for PD. The objective of this study was to investigate the contribution of PD risk variants to risk for PD in patients with GD1. We studied 225 patients with GD1, including 199 without PD and 26 with PD. All cases were genotyped, and the genetic data were imputed using common pipelines. On average, patients with GD1 with PD have a significantly higher PD genetic risk score than those without PD (P = 0.021). Our results indicate that variants included in the PD genetic risk score were more frequent in patients with GD1 who developed PD, suggesting that common risk variants may affect underlying biological pathways. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Sections du résumé
BACKGROUND
Biallelic pathogenic variants in GBA1 are the cause of Gaucher disease (GD) type 1 (GD1), a lysosomal storage disorder resulting from deficient glucocerebrosidase. Heterozygous GBA1 variants are also a common genetic risk factor for Parkinson's disease (PD). GD manifests with considerable clinical heterogeneity and is also associated with an increased risk for PD.
OBJECTIVE
The objective of this study was to investigate the contribution of PD risk variants to risk for PD in patients with GD1.
METHODS
We studied 225 patients with GD1, including 199 without PD and 26 with PD. All cases were genotyped, and the genetic data were imputed using common pipelines.
RESULTS
On average, patients with GD1 with PD have a significantly higher PD genetic risk score than those without PD (P = 0.021).
CONCLUSIONS
Our results indicate that variants included in the PD genetic risk score were more frequent in patients with GD1 who developed PD, suggesting that common risk variants may affect underlying biological pathways. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Identifiants
pubmed: 36869417
doi: 10.1002/mds.29342
pmc: PMC10271962
mid: NIHMS1868698
doi:
Substances chimiques
Glucosylceramidase
EC 3.2.1.45
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
899-903Subventions
Organisme : Intramural NIH HHS
ID : Z99 AG999999
Pays : United States
Informations de copyright
© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
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