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Genetics of Parkinson's disease.
Mol Cell Probes. 2016 12; 30(6):386-396.MC

Abstract

Almost two decades after the identification of SNCA as the first causative gene in Parkinson's disease (PD) and the subsequent understanding that genetic factors play a substantial role in PD development, our knowledge of the genetic architecture underlying this disease has vastly improved. Approximately 5-10% of patients suffer from a monogenic form of PD where autosomal dominant mutations in SNCA, LRRK2, and VPS35 and autosomal recessive mutations in PINK1, DJ-1, and Parkin cause the disease with high penetrance. Furthermore, recent whole-exome sequencing have described autosomal recessive DNAJC6 mutations in predominately atypical, but also cases with typical PD. In addition, several other genes have been linked to atypical Parkinsonian phenotypes. However, the vast majority of PD is genetically complex, i.e. it is caused by the combined action of common genetic variants in concert with environmental factors. By the application of genome-wide association studies, 26 PD risk loci have been established to date. Similar to other genetically complex diseases, these show only moderate effects on PD risk. Increasing this etiologic complexity, many of the involved genetic and environmental risk factors likely interact in an intricate fashion. This article aims to provide a comprehensive overview of the current knowledge in PD genetics.

Authors+Show Affiliations

Genetic and Molecular Epidemiology Group, Institute of Neurogenetics, University of Lübeck, Maria-Goeppert-Str. 1, 23562, Lübeck, Germany. Electronic address: christina.lill@uni-luebeck.de.

Pub Type(s)

Journal Article
Review
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27818248

Citation

Lill, Christina M.. "Genetics of Parkinson's Disease." Molecular and Cellular Probes, vol. 30, no. 6, 2016, pp. 386-396.
Lill CM. Genetics of Parkinson's disease. Mol Cell Probes. 2016;30(6):386-396.
Lill, C. M. (2016). Genetics of Parkinson's disease. Molecular and Cellular Probes, 30(6), 386-396. https://doi.org/10.1016/j.mcp.2016.11.001
Lill CM. Genetics of Parkinson's Disease. Mol Cell Probes. 2016;30(6):386-396. PubMed PMID: 27818248.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetics of Parkinson's disease. A1 - Lill,Christina M, Y1 - 2016/11/04/ PY - 2016/06/01/received PY - 2016/11/02/revised PY - 2016/11/02/accepted PY - 2016/11/8/pubmed PY - 2018/1/30/medline PY - 2016/11/8/entrez KW - Environment KW - Epidemiology KW - GWAS KW - Genetic association KW - Genetic risk score KW - Genome-wide association study KW - Interaction KW - Parkinson's disease KW - Prediction SP - 386 EP - 396 JF - Molecular and cellular probes JO - Mol Cell Probes VL - 30 IS - 6 N2 - Almost two decades after the identification of SNCA as the first causative gene in Parkinson's disease (PD) and the subsequent understanding that genetic factors play a substantial role in PD development, our knowledge of the genetic architecture underlying this disease has vastly improved. Approximately 5-10% of patients suffer from a monogenic form of PD where autosomal dominant mutations in SNCA, LRRK2, and VPS35 and autosomal recessive mutations in PINK1, DJ-1, and Parkin cause the disease with high penetrance. Furthermore, recent whole-exome sequencing have described autosomal recessive DNAJC6 mutations in predominately atypical, but also cases with typical PD. In addition, several other genes have been linked to atypical Parkinsonian phenotypes. However, the vast majority of PD is genetically complex, i.e. it is caused by the combined action of common genetic variants in concert with environmental factors. By the application of genome-wide association studies, 26 PD risk loci have been established to date. Similar to other genetically complex diseases, these show only moderate effects on PD risk. Increasing this etiologic complexity, many of the involved genetic and environmental risk factors likely interact in an intricate fashion. This article aims to provide a comprehensive overview of the current knowledge in PD genetics. SN - 1096-1194 UR - https://www.unboundmedicine.com/medline/citation/27818248/Genetics_of_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0890-8508(16)30103-7 DB - PRIME DP - Unbound Medicine ER -