Genetic Risk Profiling in Parkinson’s Disease and Utilizing Genetics to Gain Insight into Disease-Related Biological Pathways
Parkinson’s disease (PD) is a complex disorder underpinned by both environmental and genetic factors. The latter only began to be understood around two decades ago, but since then great inroads have rapidly been made into deconvoluting the genetic component of PD. In particular, recent large-scale p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/19/7332 |
| _version_ | 1797551833159303168 |
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| author | Ashley Hall Sara Bandres-Ciga Monica Diez-Fairen John P. Quinn Kimberley J. Billingsley |
| author_facet | Ashley Hall Sara Bandres-Ciga Monica Diez-Fairen John P. Quinn Kimberley J. Billingsley |
| author_sort | Ashley Hall |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is a complex disorder underpinned by both environmental and genetic factors. The latter only began to be understood around two decades ago, but since then great inroads have rapidly been made into deconvoluting the genetic component of PD. In particular, recent large-scale projects such as genome-wide association (GWA) studies have provided insight into the genetic risk factors associated with genetically ‘’complex’’ PD (PD that cannot readily be attributed to single deleterious mutations). Here, we discuss the plethora of genetic information provided by PD GWA studies and how this may be utilized to generate polygenic risk scores (PRS), which may be used in the prediction of risk and trajectory of PD. We also comment on how pathway-specific genetic profiling can be used to gain insight into PD-related biological pathways, and how this may be further utilized to nominate causal PD genes and potentially druggable therapeutic targets. Finally, we outline the current limits of our understanding of PD genetics and the potential contribution of variation currently uncaptured in genetic studies, focusing here on uncatalogued structural variants. |
| first_indexed | 2024-03-10T15:50:40Z |
| format | Article |
| id | doaj.art-5bc9616bc3ce4a68ab3dab964eadac42 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:50:40Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5bc9616bc3ce4a68ab3dab964eadac422023-11-20T16:02:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012119733210.3390/ijms21197332Genetic Risk Profiling in Parkinson’s Disease and Utilizing Genetics to Gain Insight into Disease-Related Biological PathwaysAshley Hall0Sara Bandres-Ciga1Monica Diez-Fairen2John P. Quinn3Kimberley J. Billingsley4Department of Pharmacology and Therapeutics, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, L69 7BE, UKMolecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USANeurogenetics Group, University Hospital MutuaTerrassa, Sant Antoni 19, 08221 Terrassa, Barcelona, SpainDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, L69 7BE, UKMolecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USAParkinson’s disease (PD) is a complex disorder underpinned by both environmental and genetic factors. The latter only began to be understood around two decades ago, but since then great inroads have rapidly been made into deconvoluting the genetic component of PD. In particular, recent large-scale projects such as genome-wide association (GWA) studies have provided insight into the genetic risk factors associated with genetically ‘’complex’’ PD (PD that cannot readily be attributed to single deleterious mutations). Here, we discuss the plethora of genetic information provided by PD GWA studies and how this may be utilized to generate polygenic risk scores (PRS), which may be used in the prediction of risk and trajectory of PD. We also comment on how pathway-specific genetic profiling can be used to gain insight into PD-related biological pathways, and how this may be further utilized to nominate causal PD genes and potentially druggable therapeutic targets. Finally, we outline the current limits of our understanding of PD genetics and the potential contribution of variation currently uncaptured in genetic studies, focusing here on uncatalogued structural variants.https://www.mdpi.com/1422-0067/21/19/7332Parkinson’s diseasegenetic riskbiological pathways |
| spellingShingle | Ashley Hall Sara Bandres-Ciga Monica Diez-Fairen John P. Quinn Kimberley J. Billingsley Genetic Risk Profiling in Parkinson’s Disease and Utilizing Genetics to Gain Insight into Disease-Related Biological Pathways International Journal of Molecular Sciences Parkinson’s disease genetic risk biological pathways |
| title | Genetic Risk Profiling in Parkinson’s Disease and Utilizing Genetics to Gain Insight into Disease-Related Biological Pathways |
| title_full | Genetic Risk Profiling in Parkinson’s Disease and Utilizing Genetics to Gain Insight into Disease-Related Biological Pathways |
| title_fullStr | Genetic Risk Profiling in Parkinson’s Disease and Utilizing Genetics to Gain Insight into Disease-Related Biological Pathways |
| title_full_unstemmed | Genetic Risk Profiling in Parkinson’s Disease and Utilizing Genetics to Gain Insight into Disease-Related Biological Pathways |
| title_short | Genetic Risk Profiling in Parkinson’s Disease and Utilizing Genetics to Gain Insight into Disease-Related Biological Pathways |
| title_sort | genetic risk profiling in parkinson s disease and utilizing genetics to gain insight into disease related biological pathways |
| topic | Parkinson’s disease genetic risk biological pathways |
| url | https://www.mdpi.com/1422-0067/21/19/7332 |
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