ArticleBrain : a journal of neurology2017
Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease.
Article in Brain : a journal of neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 267 papers, 4 of them syntheses that pooled it.
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Who cites it
267 citing papers in PubMed, 4 syntheses or guidelines pooled it, 445 citations in OpenAlex.
- Meta-analysis of the association of prosaposin polymorphisms rs4747203 and rs885828 with risk of Parkinson's disease.Acta neurologica Belgica · 2024Pooled it
- Association of Rare Variants in ARSA with Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2023Pooled it
- GALC variants affect galactosylceramidase enzymatic activity and risk of Parkinson's disease.Brain : a journal of neurology · 2023Pooled it
- Role of Lysosomal Gene Variants in Modulating GBA-Associated Parkinson's Disease Risk.Movement disorders : official journal of the Movement Disorder Society · 2022Pooled it
- CHCHD2 mitigates age-associated proteostatic collapse by maintaining homeostasis of the mitochondria-lysosome axis.Acta neuropathologica · 2026Article
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- Rare-Variant Burden across Lysosomal Genes Implicates Sialylation and Ganglioside Metabolism in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Roles of autophagy in brain homeostasis and disease.Nature neuroscience · 2026Review
- Metabolomic signatures for diagnosis and clinical severity in Parkinson's disease.EBioMedicine · 2026Article
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- Circulating extracellular vesicles in plasma carry accessible molecular signatures of aging in mice.bioRxiv : the preprint server for biology · 2026Article
- A human lysosomal storage disorder toolkit for decoding proteome landscapes in cortical-like and dopaminergic-like induced neurons.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Lysine acetyltransferase 8-mediated histone acetylation, regulated by GBA1, is associated with lysosomal function related to α-Synuclein pathology.Cell death & disease · 2026Article
- Preformed fibrils of α-synuclein rapidly activate LRRK2 on early endosomes, driving Rab5 phosphorylation and disrupting endolysosomal and synaptic function.NPJ Parkinson's disease · 2026Article
- Blood-Brain Network-Based Polygenic Risk Scores Reveal Biomarker Signatures and the Progression of Alzheimer's Disease.Journal of clinical medicine · 2026Article
- Metabolic profiles associated with fat loss in Parkinson's disease.Journal of neurology, neurosurgery, and psychiatry · 2026Article
- Subtle cellular phenotypes inform pathological and benign genetic mutants in the Iduronate-2 sulfatase gene.Human molecular genetics · 2026Article
- Rare-variant burden across lysosomal genes implicates sialylation and ganglioside metabolism in Parkinson's disease.medRxiv : the preprint server for health sciences · 2026Article
- Two lysosomal genes ATP13A2 and GBA1 interact to drive neurodegeneration.Molecular neurodegeneration · 2026Article
- RNA networks of lysosomal-related biomarkers in Parkinson's disease and their correlations with freezing of gait-associated genes.Frontiers in genetics · 2026Article
207 more citing papers are in PubMed but not listed here.
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9 authors at 3 institutions in 3 countries.
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Abstract
Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants in other lysosomal storage disorder genes is more broadly associated with Parkinson's disease susceptibility. The sequence kernel association test was used to interrogate variant burden among 54 lysosomal storage disorder genes, leveraging whole exome sequencing data from 1156 Parkinson's disease cases and 1679 control subjects. We discovered a significant burden of rare, likely damaging lysosomal storage disorder gene variants in association with Parkinson's disease risk. The association signal was robust to the exclusion of GBA, and consistent results were obtained in two independent replication cohorts, including 436 cases and 169 controls with whole exome sequencing and an additional 6713 cases and 5964 controls with exome-wide genotyping. In secondary analyses designed to highlight the specific genes driving the aggregate signal, we confirmed associations at the GBA and SMPD1 loci and newly implicate CTSD, SLC17A5, and ASAH1 as candidate Parkinson's disease susceptibility genes. In our discovery cohort, the majority of Parkinson's disease cases (56%) have at least one putative damaging variant in a lysosomal storage disorder gene, and 21% carry multiple alleles. Our results highlight several promising new susceptibility loci and reinforce the importance of lysosomal mechanisms in Parkinson's disease pathogenesis. We suggest that multiple genetic hits may act in combination to degrade lysosomal function, enhancing Parkinson's disease susceptibility.
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Registered trials
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.