The genetic architecture of Parkinson's disease
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 o...
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| Veröffentlicht in: | Lancet neurology Jg. 19; H. 2; S. 170 - 178 |
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| Hauptverfasser: | , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
England
Elsevier Ltd
01.02.2020
Elsevier Limited |
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| ISSN: | 1474-4422, 1474-4465, 1474-4465 |
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| Abstract | 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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| AbstractList | 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. 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.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. Summary 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. |
| Author | Singleton, Andrew B Blauwendraat, Cornelis Nalls, Mike A |
| Author_xml | – sequence: 1 givenname: Cornelis surname: Blauwendraat fullname: Blauwendraat, Cornelis email: cornelis.blauwendraat@nih.gov organization: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA – sequence: 2 givenname: Mike A surname: Nalls fullname: Nalls, Mike A organization: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA – sequence: 3 givenname: Andrew B surname: Singleton fullname: Singleton, Andrew B email: singleta@mail.nih.gov organization: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31521533$$D View this record in MEDLINE/PubMed |
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| Copyright | 2020 Elsevier Ltd Copyright © 2020 Elsevier Ltd. All rights reserved. 2020. Elsevier Ltd |
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| Snippet | Parkinson's disease is a complex neurodegenerative disorder for which both rare and common genetic variants contribute to disease risk, onset, and progression.... Summary Parkinson's disease is a complex neurodegenerative disorder for which both rare and common genetic variants contribute to disease risk, onset, and... Parkinson’s disease is a complex neurodegenerative disorder for which both rare and common genetic variants contribute to disease risk, onset, and progression.... |
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| SubjectTerms | Alleles Dementia - genetics Deoxyribonucleic acid Disease Progression DNA Genes Genetic diversity Genetic Predisposition to Disease - genetics Genetic variability Genetics Genome-wide association studies Genome-Wide Association Study Genomes Humans Kinases Learning algorithms Movement disorders Mutation Mutation - genetics Neurodegenerative diseases Neurodegenerative Diseases - diagnosis Neurodegenerative Diseases - genetics Parkinson Disease - diagnosis Parkinson Disease - genetics Parkinson's disease Ribonucleic acid Risk Factors RNA |
| Title | The genetic architecture of Parkinson's disease |
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