Association of Rare Variants in ARSA with Parkinson's Disease.
ARSA
Parkinson's disease
lysosomal genes
rare variants
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:
10 2023
10 2023
Historique:
revised:
25
05
2023
received:
06
03
2023
accepted:
12
06
2023
pmc-release:
01
10
2024
medline:
30
10
2023
pubmed:
29
6
2023
entrez:
29
6
2023
Statut:
ppublish
Résumé
Several lysosomal genes are associated with Parkinson's disease (PD), yet the association between PD and ARSA remains unclear. To study rare ARSA variants in PD. To study rare ARSA variants (minor allele frequency < 0.01) in PD, we performed burden analyses in six independent cohorts with 5801 PD patients and 20,475 controls, followed by a meta-analysis. We found evidence for associations between functional ARSA variants and PD in four cohorts (P ≤ 0.05 in each) and in the meta-analysis (P = 0.042). We also found an association between loss-of-function variants and PD in the United Kingdom Biobank cohort (P = 0.005) and in the meta-analysis (P = 0.049). These results should be interpreted with caution as no association survived multiple comparisons correction. Additionally, we describe two families with potential co-segregation of ARSA p.E382K and PD. Rare functional and loss-of-function ARSA variants may be associated with PD. Further replications in large case-control/familial cohorts are required. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Sections du résumé
BACKGROUND
Several lysosomal genes are associated with Parkinson's disease (PD), yet the association between PD and ARSA remains unclear.
OBJECTIVES
To study rare ARSA variants in PD.
METHODS
To study rare ARSA variants (minor allele frequency < 0.01) in PD, we performed burden analyses in six independent cohorts with 5801 PD patients and 20,475 controls, followed by a meta-analysis.
RESULTS
We found evidence for associations between functional ARSA variants and PD in four cohorts (P ≤ 0.05 in each) and in the meta-analysis (P = 0.042). We also found an association between loss-of-function variants and PD in the United Kingdom Biobank cohort (P = 0.005) and in the meta-analysis (P = 0.049). These results should be interpreted with caution as no association survived multiple comparisons correction. Additionally, we describe two families with potential co-segregation of ARSA p.E382K and PD.
CONCLUSIONS
Rare functional and loss-of-function ARSA variants may be associated with PD. Further replications in large case-control/familial cohorts are required. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Identifiants
pubmed: 37381728
doi: 10.1002/mds.29521
pmc: PMC10615669
mid: NIHMS1914494
doi:
Substances chimiques
Cerebroside-Sulfatase
EC 3.1.6.8
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1806-1812Subventions
Organisme : NINDS NIH HHS
ID : K02 NS080915
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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