Multi-omic insights into Parkinson's Disease: From genetic associations to functional mechanisms
Genome-Wide Association Studies (GWAS) have elucidated the genetic components of Parkinson's Disease (PD). However, because the vast majority of GWAS association signals fall within non-coding regions, translating these results into an interpretable, mechanistic understanding of the disease eti...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-02-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996121003296 |
| _version_ | 1818942854284705792 |
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| author | Brian M. Schilder Elisa Navarro Towfique Raj |
| author_facet | Brian M. Schilder Elisa Navarro Towfique Raj |
| author_sort | Brian M. Schilder |
| collection | DOAJ |
| description | Genome-Wide Association Studies (GWAS) have elucidated the genetic components of Parkinson's Disease (PD). However, because the vast majority of GWAS association signals fall within non-coding regions, translating these results into an interpretable, mechanistic understanding of the disease etiology remains a major challenge in the field. In this review, we provide an overview of the approaches to prioritize putative causal variants and genes as well as summarise the primary findings of previous studies. We then discuss recent efforts to integrate multi-omics data to identify likely pathogenic cell types and biological pathways implicated in PD pathogenesis. We have compiled full summary statistics of cell-type, tissue, and phentoype enrichment analyses from multiple studies of PD GWAS and provided them in a standardized format as a resource for the research community (https://github.com/RajLabMSSM/PD_omics_review). Finally, we discuss the experimental, computational, and conceptual advances that will be necessary to fully elucidate the effects of functional variants and genes on cellular dysregulation and disease risk. |
| first_indexed | 2024-12-20T07:18:03Z |
| format | Article |
| id | doaj.art-2b877f6768904191a1ed53ac502c4213 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-20T07:18:03Z |
| publishDate | 2022-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-2b877f6768904191a1ed53ac502c42132022-12-21T19:48:45ZengElsevierNeurobiology of Disease1095-953X2022-02-01163105580Multi-omic insights into Parkinson's Disease: From genetic associations to functional mechanismsBrian M. Schilder0Elisa Navarro1Towfique Raj2Nash Family Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Ronald M. Loeb Center for Alzheimer's disease, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Estelle and Daniel Maggin Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom; UK Dementia Research Institute at Imperial College London, London, United Kingdom; Correspondence to: B.M. Schilder, 86 Wood Ln, Sir Michael Uren Hub, 7th floor, UK Dementia Research Institute, Imperial College London, London W12 0BZ, United Kingdom.Nash Family Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Ronald M. Loeb Center for Alzheimer's disease, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Estelle and Daniel Maggin Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Sección Departamental de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, SpainNash Family Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Ronald M. Loeb Center for Alzheimer's disease, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Estelle and Daniel Maggin Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Correspondence to: T. Raj, 1425 Madison Avenue, Icahn 10-70E, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, United States.Genome-Wide Association Studies (GWAS) have elucidated the genetic components of Parkinson's Disease (PD). However, because the vast majority of GWAS association signals fall within non-coding regions, translating these results into an interpretable, mechanistic understanding of the disease etiology remains a major challenge in the field. In this review, we provide an overview of the approaches to prioritize putative causal variants and genes as well as summarise the primary findings of previous studies. We then discuss recent efforts to integrate multi-omics data to identify likely pathogenic cell types and biological pathways implicated in PD pathogenesis. We have compiled full summary statistics of cell-type, tissue, and phentoype enrichment analyses from multiple studies of PD GWAS and provided them in a standardized format as a resource for the research community (https://github.com/RajLabMSSM/PD_omics_review). Finally, we discuss the experimental, computational, and conceptual advances that will be necessary to fully elucidate the effects of functional variants and genes on cellular dysregulation and disease risk.http://www.sciencedirect.com/science/article/pii/S0969996121003296Parkinson's DiseaseNeurodegenerationGenome-wide association study (GWAS)Quantitative trait loci (QTL)Multi-omicsMeta-analysis |
| spellingShingle | Brian M. Schilder Elisa Navarro Towfique Raj Multi-omic insights into Parkinson's Disease: From genetic associations to functional mechanisms Neurobiology of Disease Parkinson's Disease Neurodegeneration Genome-wide association study (GWAS) Quantitative trait loci (QTL) Multi-omics Meta-analysis |
| title | Multi-omic insights into Parkinson's Disease: From genetic associations to functional mechanisms |
| title_full | Multi-omic insights into Parkinson's Disease: From genetic associations to functional mechanisms |
| title_fullStr | Multi-omic insights into Parkinson's Disease: From genetic associations to functional mechanisms |
| title_full_unstemmed | Multi-omic insights into Parkinson's Disease: From genetic associations to functional mechanisms |
| title_short | Multi-omic insights into Parkinson's Disease: From genetic associations to functional mechanisms |
| title_sort | multi omic insights into parkinson s disease from genetic associations to functional mechanisms |
| topic | Parkinson's Disease Neurodegeneration Genome-wide association study (GWAS) Quantitative trait loci (QTL) Multi-omics Meta-analysis |
| url | http://www.sciencedirect.com/science/article/pii/S0969996121003296 |
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