ArticleMovement disorders : official journal of the Movement Disorder Society2019
SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson's Disease.
Article in Movement disorders : official journal of the Movement Disorder Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Common SNCA Genetic Variants and Parkinson's Disease Risk: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2025Pooled it
- Individualized Bayesian Inference Identifies Novel Genetic Variants for Parkinson's Disease.Genetic epidemiology · 2026Article
- Semiparametric efficient estimation of small genetic effects in large-scale population cohorts.Biostatistics (Oxford, England) · 2025Article
- Genome-wide epistasis analysis reveals significant epistatic signals associated with Parkinson's disease risk.Brain : a journal of neurology · 2025Article
- Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens.Human genomics · 2024Review
- Genetic Analysis of Neurite Outgrowth Inhibitor-Associated Genes in Parkinson's Disease: A Cross-Sectional Cohort Study.CNS neuroscience & therapeutics · 2024Article
- Genome-wide case-only analysis of gene-gene interactions with known Parkinson's disease risk variants reveals link between LRRK2 and SYT10.NPJ Parkinson's disease · 2023Article
- Review
- High content screening and proteomic analysis identify a kinase inhibitor that rescues pathological phenotypes in a patient-derived model of Parkinson's disease.NPJ Parkinson's disease · 2022Article
- Unraveling Parkinson's Disease Neurodegeneration: Does Aging Hold the Clues?Journal of Parkinson's disease · 2022Review
- Platelet miRNA Biosignature Discriminates between Dementia with Lewy Bodies and Alzheimer's Disease.Biomedicines · 2021Article
- Characterizing the Genetic Architecture of Parkinson's Disease in Latinos.Annals of neurology · 2021Article
- A systematic review of associations between common SNCA variants and clinical heterogeneity in Parkinson's disease.NPJ Parkinson's disease · 2021Review
- Association Analyses ofNeuropsychiatric disease and treatment · 2021Article
- Crocin Reverses Depression-Like Behavior in Parkinson Disease Mice via VTA-mPFC Pathway.Molecular neurobiology · 2020Article
- Genetics of Parkinson's disease: An introspection of its journey towards precision medicine.Neurobiology of disease · 2020Review
- Metal Exposure and SNCA rs356219 Polymorphism Associated With Parkinson Disease and Parkinsonism.Frontiers in neurology · 2020Article
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundSingle nucleotide polymorphisms (SNPs) in the α-synuclein (SNCA) gene are associated with differential risk and age at onset (AAO) of both idiopathic and Leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson's disease (PD). Yet potential combinatory or synergistic effects among several modulatory SNPs for PD risk or AAO remain largely underexplored.
objectivesThe mechanistic target of rapamycin (mTOR) signaling pathway is functionally impaired in PD. Here we explored whether SNPs in the mTOR pathway, alone or by epistatic interaction with known susceptibility factors, can modulate PD risk and AAO.
methodsBased on functional relevance, we selected a total of 64 SNPs mapping to a total of 57 genes from the mTOR pathway and genotyped a discovery series cohort encompassing 898 PD patients and 921 controls. As a replication series, we screened 4170 PD and 3014 controls available from the International Parkinson's Disease Genomics Consortium.
resultsIn the discovery series cohort, we found a 4-loci interaction involving STK11 rs8111699, FCHSD1 rs456998, GSK3B rs1732170, and SNCA rs356219, which was associated with an increased risk of PD (odds ratio = 2.59, P < .001). In addition, we also found a 3-loci epistatic combination of RPTOR rs11868112 and RPS6KA2 rs6456121 with SNCA rs356219, which was associated (odds ratio = 2.89; P < .0001) with differential AAO. The latter was further validated (odds ratio = 1.56; P = 0.046-0.047) in the International Parkinson's Disease Genomics Consortium cohort.
conclusionsThese findings indicate that genetic variability in the mTOR pathway contributes to SNCA effects in a nonlinear epistatic manner to modulate differential AAO in PD, unraveling the contribution of this cascade in the pathogenesis of the disease. © 2019 International Parkinson and Movement Disorder Society.
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