Lim, Shen-Yang and Klein, Christine (2024) Parkinson's Disease is Predominantly a Genetic Disease. Journal of Parkinsons Disease, 14 (3). pp. 467-482. ISSN 1877-7171, DOI https://doi.org/10.3233/JPD-230376.
Full text not available from this repository.Abstract
The discovery of a pathogenic variant in the alpha-synuclein (SNCA) gene in the Contursi kindred in 1997 indisputably confirmed a genetic cause in a subset of Parkinson's disease (PD) patients. Currently, pathogenic variants in one of the seven established PD genes or the strongest known risk factor gene, GBA1, are identified in similar to 15% of PD patients unselected for age at onset and family history. In this Debate article, we highlight multiple avenues of research that suggest an important - and in some cases even predominant - role for genetics in PD aetiology, including familial clustering, high rates of monogenic PD in selected populations, and complete penetrance with certain forms. At first sight, the steep increase in PD prevalence exceeding that of other neurodegenerative diseases may argue against a predominant genetic etiology. Notably, the principal genetic contribution in PD is conferred by pathogenic variants in LRRK2 and GBA1 and, in both cases, characterized by an overall late age of onset and age-related penetrance. In addition, polygenic risk plays a considerable role in PD. However, it is likely that, in the majority of PD patients, a complex interplay of aging, genetic, environmental, and epigenetic factors leads to disease development.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Higher Education Malaysia Fundamental Research Grant Scheme (FRGS/1/2020/SKK0/UM/01/2), University of Malaya Parkinson's Disease and Movement Disorders Research Program (PV035-2017), Global Parkinson's Genetics Program, Aligning Science Across Parkinson's (ASAP), German Research Foundation (DFG), MJFF |
| Uncontrolled Keywords: | Parkinson's disease; genetics; monogenic; polygenic; familial; GBA1; LRRK2; PRKN; environment; geneenvironment; interactions; epigenetic; progression; pandemic |
| Subjects: | R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry |
| Divisions: | Faculty of Medicine > Medicine Department |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 13 Nov 2024 04:54 |
| Last Modified: | 13 Nov 2024 04:54 |
| URI: | http://eprints.um.edu.my/id/eprint/45875 |
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