ArticleMovement disorders : official journal of the Movement Disorder Society2020
Common Variants Coregulate Expression of GBA and Modifier Genes to Delay Parkinson's Disease Onset.
Article in Movement disorders : official journal of the Movement Disorder Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Establishing gene regulatory networks from Parkinson's disease risk loci.Brain : a journal of neurology · 2022Pooled it
- Clinical, biochemical and molecular spectrum of acute neuronopathic type 2 Gaucher disease from India.BMC pediatrics · 2026Article
- Article
- Identification of 27 allele-specific regulatory variants in Parkinson's disease using a massively parallel reporter assay.NPJ Parkinson's disease · 2024Article
- GBA1 Variants and Parkinson's Disease: Paving the Way for Targeted Therapy.Journal of movement disorders · 2023Article
- Genetic meta-analysis of levodopa induced dyskinesia in Parkinson's disease.NPJ Parkinson's disease · 2023Article
- Mechanisms of Glucocerebrosidase Dysfunction in Parkinson's Disease.Journal of molecular biology · 2023Review
- Genetic meta-analysis of levodopa induced dyskinesia in Parkinson's disease.medRxiv : the preprint server for health sciences · 2023Article
- A severe neurodegenerative disease with Lewy bodies and a mutation in the glucocerebrosidase gene.NPJ Parkinson's disease · 2023Article
- Article
- Transcriptome deregulation of peripheral monocytes and whole blood in GBA-related Parkinson's disease.Molecular neurodegeneration · 2022Article
- Comprehensive short and long read sequencing analysis for the Gaucher and Parkinson's disease-associated GBA gene.Communications biology · 2022Article
- Redefining the hypotheses driving Parkinson's diseases research.NPJ Parkinson's disease · 2022Review
- Glycosphingolipid metabolism and its role in ageing and Parkinson's disease.Glycoconjugate journal · 2022Review
- Glucocerebrosidase Activity is not Associated with Parkinson's Disease Risk or Severity.Movement disorders : official journal of the Movement Disorder Society · 2022Article
- Intronic Haplotypes in the GBA Gene Do Not Predict Age at Diagnosis of Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2021Article
- The Role of Cholesterol in α-Synuclein and Lewy Body Pathology in GBA1 Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2021Review
- Advancing Personalized Medicine in Common Forms of Parkinson's Disease through Genetics: Current Therapeutics and the Future of Individualized Management.Journal of personalized medicine · 2021Review
- Exploring the Genotype-Phenotype Correlation inFrontiers in neurology · 2021Review
- Machine Learning Identifies Six Genetic Variants and Alterations in the Heart Atrial Appendage as Key Contributors to PD Risk Predictivity.Frontiers in genetics · 2021Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGBA mutations are numerically the most significant genetic risk factor for Parkinson's disease (PD), yet these mutations have low penetrance, suggesting additional mechanisms.
objectivesThe objective of this study was to determine if the penetrance of GBA in PD can be explained by regulatory effects on GBA and modifier genes.
methodsGenetic variants associated with the regulation of GBA were identified by screening 128 common single nucleotide polymorphisms (SNPs) in the GBA locus for spatial cis-expression quantitative trail locus (supported by chromatin interactions).
resultsWe identified common noncoding SNPs within GBA that (1) regulate GBA expression in peripheral tissues, some of which display α-synuclein pathology and (2) coregulate potential modifier genes in the central nervous system and/or peripheral tissues. Haplotypes based on 3 of these SNPs delay disease onset by 5 years. In addition, SNPs on 6 separate chromosomes coregulate GBA expression specifically in either the substantia nigra or cortex, and their combined effect potentially modulates motor and cognitive symptoms, respectively.
conclusionsThis work provides a new perspective on the haplotype-specific effects of GBA and the genetic etiology of PD, expanding the role of GBA from the gene encoding the β-glucocerebrosidase (GCase) to that of a central regulator and modifier of PD onset, with GBA expression itself subject to distant regulation. Some idiopathic patients might possess insufficient GBA-encoded GCase activity in the substantia nigra as the result of distant regulatory variants and therefore might benefit from GBA-targeting therapeutics. The SNPs' regulatory impacts provide a plausible explanation for the variable phenotypes also observed in GBA-centric Gaucher's disease and dementia with Lewy bodies. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, LLC on behalf of International Parkinson and Movement Disorder Society.
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