SynthesisMovement disorders : official journal of the Movement Disorder Society2022
Role of Lysosomal Gene Variants in Modulating GBA-Associated Parkinson's Disease Risk.
Synthesis in Movement disorders : official journal of the Movement Disorder Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Two lysosomal genes ATP13A2 and GBA1 interact to drive neurodegeneration.Molecular neurodegeneration · 2026Article
- A Common PD-RiskbioRxiv : the preprint server for biology · 2025Article
- Genome-Wide Association Study of Glucocerebrosidase Activity Modifiers.Molecular neurobiology · 2025Article
- Targeting chaperone-mediated autophagy in neurodegenerative diseases: mechanisms and therapeutic potential.Acta pharmacologica Sinica · 2025Review
- Early-onset Parkinson's disease in a patient with a rare homozygous pathogenic GBA1 variant and no Gaucher disease symptoms.Neurogenetics · 2025Article
- Article
- Comparing GBA1-Parkinson's disease and idiopathic Parkinson's disease: α-Synuclein oligomers and synaptic density as biomarkers in the skin biopsy.Brain pathology (Zurich, Switzerland) · 2024Article
- Clinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson's disease.Translational neurodegeneration · 2024Review
- Biochemical consequences ofNeural regeneration research · 2024Article
- IsmedRxiv : the preprint server for health sciences · 2024Article
- GBA1 Variants and Parkinson's Disease: Paving the Way for Targeted Therapy.Journal of movement disorders · 2023Article
- Mechanisms of Glucocerebrosidase Dysfunction in Parkinson's Disease.Journal of molecular biology · 2023Review
- Functional screening of lysosomal storage disorder genes identifies modifiers of alpha-synuclein neurotoxicity.PLoS genetics · 2023Article
- Who is at Risk of Parkinson Disease? Refining the Preclinical Phase of GBA1 and LRRK2 Variant Carriers: a Clinical, Biochemical, and Imaging Approach.Current neurology and neuroscience reports · 2023Review
- Genetic Evidence for Endolysosomal Dysfunction in Parkinson's Disease: A Critical Overview.International journal of molecular sciences · 2023Review
- Genetics and Pathogenesis of Parkinson's Syndrome.Annual review of pathology · 2023Review
- Sphingolipids in neurodegenerative diseases.Frontiers in neuroscience · 2023Review
- A Mouse Model to Test Novel Therapeutics for Parkinson's Disease: an Update on the Thy1-aSyn ("line 61") Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- GBA1 and The Immune System: A Potential Role in Parkinson's Disease?Journal of Parkinson's disease · 2022Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundTo date, variants in the GBA gene represent the most frequent large-effect genetic factor associated with Parkinson's disease (PD). However, the reason why individuals with the same GBA variant may or may not develop neurodegeneration and PD is still unclear.
objectivesTherefore, we evaluated the contribution of rare variants in genes responsible for lysosomal storage disorders (LSDs) to GBA-PD risk, comparing the burden of deleterious variants in LSD genes in PD patients versus asymptomatic subjects, all carriers of deleterious variants in GBA.
methodsWe used a custom next-generation sequencing panel, including 50 LSD genes, to screen 305 patients and 207 controls (discovery cohort). Replication and meta-analysis were performed in two replication cohorts of GBA-variant carriers, of 250 patients and 287 controls, for whom exome or genome data were available.
resultsStatistical analysis in the discovery cohort revealed a significantly increased burden of deleterious variants in LSD genes in patients (P = 0.0029). Moreover, our analyses evidenced that the two strongest modifiers of GBA penetrance are a second variation in GBA (5.6% vs. 1.4%, P = 0.023) and variants in genes causing mucopolysaccharidoses (6.9% vs. 1%, P = 0.0020). These results were confirmed in the meta-analysis, where we observed pooled odds ratios of 1.42 (95% confidence interval [CI] = 1.10-1.83, P = 0.0063), 4.36 (95% CI = 2.02-9.45, P = 0.00019), and 1.83 (95% CI = 1.04-3.22, P = 0.038) for variants in LSD genes, GBA, and mucopolysaccharidosis genes, respectively.
conclusionThe identification of genetic lesions in lysosomal genes increasing PD risk may have important implications in terms of patient stratification for future therapeutic trials. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.