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The genetic architecture of Parkinson's disease
Open accessAbstract
Parkinson's disease is a complex neurodegenerative disorder for which both rare and common genetic variants contribute to disease risk, onset, and progression. Mutations in more than 20 genes have been associated with the disease, most of which are highly penetrant and often cause early onset or atypical symptoms. Although our understanding of the genetic basis of Parkinson's disease has advanced considerably, much remains to be done. Further disease-related common genetic variability remains to be identified and the work in identifying rare risk alleles has only just begun. To date, genome-wide association studies have identified 90 independent risk-associated variants. However, most of them have been identified in patients of European ancestry and we know relatively little of the genetics of Parkinson's disease in other populations. We have a limited understanding of the biological functions of the risk alleles that have been identified, although Parkinson's disease risk variants appear to be in close proximity to known Parkinson's disease genes and lysosomal-related genes. In the past decade, multiple efforts have been made to investigate the genetic architecture of Parkinson's disease, and emerging technologies, such as machine learning, single-cell RNA sequencing, and high-throughput screens, will improve our understanding of genetic risk.
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Mutations in SNCA have been proposed to cause aberrant conformation in α-syn, resulting in enhanced conversion of soluble α-syn into insoluble aggregates identified in PD.
“mutations in SNCA have been proposed to cause aberrant conformation in α-syn, resulting in enhanced conversion of soluble α-syn into insoluble aggregates identified in PD.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [256]
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Metadata
- Authors
- Blauwendraat, C., Nalls, M. A., & Singleton, A. B.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Blauwendraat, Cornelis
- Singleton, Andrew B
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 19
- Issue
- 2
- Pages
- 170-178
- ISSN
- 1474-4422 (ISSN-L)
- PMC
- PMC8972299
- OpenAlex
- W2972937106
- Cited by
- 1,114
- References
- 73
- Citations by year
- 2026: 133 · 2025: 188 · 2024: 216 · 2023: 181 · 2022: 169 · 2021: 145 · 2020: 80
- FWCI
- 13.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- American Bureau of Shipping
- National Institute on Aging
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, genetic architecture, genetic risk variants, rare genetic mutations, common genetic variants, genome-wide association study, lysosomal genes, genetic ancestry, neurodegeneration, disease progression
- MeSH terms
- Dementia, Humans, Mutation, Parkinson Disease, Risk Factors, Disease Progression, Neurodegenerative Diseases, Genetic Predisposition to Disease, Genome-Wide Association Study
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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