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.
Keywords: ARSA; Parkinson's disease; lysosomal genes; rare variants.
© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.