DNA methylation as a mediator of genetic and environmental influences on Parkinson’s disease susceptibility: Impacts of alpha-Synuclein, physical activity, and pesticide exposure on the epigenome
Parkinson’s disease (PD) is a neurodegenerative disorder with a complex etiology and increasing prevalence worldwide. As PD is influenced by a combination of genetic and environment/lifestyle factors in approximately 90% of cases, there is increasing interest in identification of the interindividual...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.971298/full |
| _version_ | 1798037603990110208 |
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| author | Samantha L. Schaffner Samantha L. Schaffner Michael S. Kobor Michael S. Kobor |
| author_facet | Samantha L. Schaffner Samantha L. Schaffner Michael S. Kobor Michael S. Kobor |
| author_sort | Samantha L. Schaffner |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is a neurodegenerative disorder with a complex etiology and increasing prevalence worldwide. As PD is influenced by a combination of genetic and environment/lifestyle factors in approximately 90% of cases, there is increasing interest in identification of the interindividual mechanisms underlying the development of PD as well as actionable lifestyle factors that can influence risk. This narrative review presents an outline of the genetic and environmental factors contributing to PD risk and explores the possible roles of cytosine methylation and hydroxymethylation in the etiology and/or as early-stage biomarkers of PD, with an emphasis on epigenome-wide association studies (EWAS) of PD conducted over the past decade. Specifically, we focused on variants in the SNCA gene, exposure to pesticides, and physical activity as key contributors to PD risk. Current research indicates that these factors individually impact the epigenome, particularly at the level of CpG methylation. There is also emerging evidence for interaction effects between genetic and environmental contributions to PD risk, possibly acting across multiple omics layers. We speculated that this may be one reason for the poor replicability of the results of EWAS for PD reported to date. Our goal is to provide direction for future epigenetics studies of PD to build upon existing foundations and leverage large datasets, new technologies, and relevant statistical approaches to further elucidate the etiology of this disease. |
| first_indexed | 2024-04-11T21:28:48Z |
| format | Article |
| id | doaj.art-bc99826742bc448d80167cb23f8a8a12 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T21:28:48Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-bc99826742bc448d80167cb23f8a8a122022-12-22T04:02:16ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.971298971298DNA methylation as a mediator of genetic and environmental influences on Parkinson’s disease susceptibility: Impacts of alpha-Synuclein, physical activity, and pesticide exposure on the epigenomeSamantha L. Schaffner0Samantha L. Schaffner1Michael S. Kobor2Michael S. Kobor3Edwin S. H. Leong Healthy Aging Program, Faculty of Medicine, University of British Columbia, Vancouver, BC, CanadaDepartment of Medical Genetics, British Columbia Children’s Hospital Research Institute, University of British Columbia, Vancouver, BC, CanadaEdwin S. H. Leong Healthy Aging Program, Faculty of Medicine, University of British Columbia, Vancouver, BC, CanadaDepartment of Medical Genetics, British Columbia Children’s Hospital Research Institute, University of British Columbia, Vancouver, BC, CanadaParkinson’s disease (PD) is a neurodegenerative disorder with a complex etiology and increasing prevalence worldwide. As PD is influenced by a combination of genetic and environment/lifestyle factors in approximately 90% of cases, there is increasing interest in identification of the interindividual mechanisms underlying the development of PD as well as actionable lifestyle factors that can influence risk. This narrative review presents an outline of the genetic and environmental factors contributing to PD risk and explores the possible roles of cytosine methylation and hydroxymethylation in the etiology and/or as early-stage biomarkers of PD, with an emphasis on epigenome-wide association studies (EWAS) of PD conducted over the past decade. Specifically, we focused on variants in the SNCA gene, exposure to pesticides, and physical activity as key contributors to PD risk. Current research indicates that these factors individually impact the epigenome, particularly at the level of CpG methylation. There is also emerging evidence for interaction effects between genetic and environmental contributions to PD risk, possibly acting across multiple omics layers. We speculated that this may be one reason for the poor replicability of the results of EWAS for PD reported to date. Our goal is to provide direction for future epigenetics studies of PD to build upon existing foundations and leverage large datasets, new technologies, and relevant statistical approaches to further elucidate the etiology of this disease.https://www.frontiersin.org/articles/10.3389/fgene.2022.971298/fullParkinson’s diseaseneurodegenerationepigeneticsDNA methylationgene-environment interaction |
| spellingShingle | Samantha L. Schaffner Samantha L. Schaffner Michael S. Kobor Michael S. Kobor DNA methylation as a mediator of genetic and environmental influences on Parkinson’s disease susceptibility: Impacts of alpha-Synuclein, physical activity, and pesticide exposure on the epigenome Frontiers in Genetics Parkinson’s disease neurodegeneration epigenetics DNA methylation gene-environment interaction |
| title | DNA methylation as a mediator of genetic and environmental influences on Parkinson’s disease susceptibility: Impacts of alpha-Synuclein, physical activity, and pesticide exposure on the epigenome |
| title_full | DNA methylation as a mediator of genetic and environmental influences on Parkinson’s disease susceptibility: Impacts of alpha-Synuclein, physical activity, and pesticide exposure on the epigenome |
| title_fullStr | DNA methylation as a mediator of genetic and environmental influences on Parkinson’s disease susceptibility: Impacts of alpha-Synuclein, physical activity, and pesticide exposure on the epigenome |
| title_full_unstemmed | DNA methylation as a mediator of genetic and environmental influences on Parkinson’s disease susceptibility: Impacts of alpha-Synuclein, physical activity, and pesticide exposure on the epigenome |
| title_short | DNA methylation as a mediator of genetic and environmental influences on Parkinson’s disease susceptibility: Impacts of alpha-Synuclein, physical activity, and pesticide exposure on the epigenome |
| title_sort | dna methylation as a mediator of genetic and environmental influences on parkinson s disease susceptibility impacts of alpha synuclein physical activity and pesticide exposure on the epigenome |
| topic | Parkinson’s disease neurodegeneration epigenetics DNA methylation gene-environment interaction |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.971298/full |
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