Mitochondrial DNA variation in Parkinson’s disease: Analysis of “out-of-place” population variants as a risk factor
Mitochondrial DNA (mtDNA), a potential source of mitochondrial dysfunction, has been implicated in Parkinson’s disease (PD). However, many previous studies investigating associations between mtDNA population variation and PD reported inconsistent or contradictory findings. Here, we investigated an a...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.921412/full |
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| author | Amica C. Müller-Nedebock Amica C. Müller-Nedebock Abigail L. Pfaff Abigail L. Pfaff Ilse S. Pienaar Sulev Kõks Sulev Kõks Francois H. van der Westhuizen Joanna L. Elson Joanna L. Elson Soraya Bardien Soraya Bardien |
| author_facet | Amica C. Müller-Nedebock Amica C. Müller-Nedebock Abigail L. Pfaff Abigail L. Pfaff Ilse S. Pienaar Sulev Kõks Sulev Kõks Francois H. van der Westhuizen Joanna L. Elson Joanna L. Elson Soraya Bardien Soraya Bardien |
| author_sort | Amica C. Müller-Nedebock |
| collection | DOAJ |
| description | Mitochondrial DNA (mtDNA), a potential source of mitochondrial dysfunction, has been implicated in Parkinson’s disease (PD). However, many previous studies investigating associations between mtDNA population variation and PD reported inconsistent or contradictory findings. Here, we investigated an alternative hypothesis to determine whether mtDNA variation could play a significant role in PD risk. Emerging evidence suggests that haplogroup-defining mtDNA variants may have pathogenic potential if they occur “out-of-place” on a different maternal lineage. We hypothesized that the mtDNA of PD cases would be enriched for out-of-place variation in genes encoding components of the oxidative phosphorylation complexes. We tested this hypothesis with a unique dataset comprising whole mitochondrial genomes of 70 African ancestry PD cases, two African ancestry control groups (n = 78 and n = 53) and a replication group of 281 European ancestry PD cases and 140 controls from the Parkinson’s Progression Markers Initiative cohort. Significantly more African ancestry PD cases had out-of-place variants than controls from the second control group (P < 0.0125), although this association was not observed in the first control group nor the replication group. As the first mtDNA study to include African ancestry PD cases and to explore out-of-place variation in a PD context, we found evidence that such variation might be significant in this context, thereby warranting further replication in larger cohorts. |
| first_indexed | 2024-04-13T04:44:43Z |
| format | Article |
| id | doaj.art-f877b442e8d1404ab7be17ae21b008da |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-13T04:44:43Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-f877b442e8d1404ab7be17ae21b008da2022-12-22T03:01:53ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-07-011410.3389/fnagi.2022.921412921412Mitochondrial DNA variation in Parkinson’s disease: Analysis of “out-of-place” population variants as a risk factorAmica C. Müller-Nedebock0Amica C. Müller-Nedebock1Abigail L. Pfaff2Abigail L. Pfaff3Ilse S. Pienaar4Sulev Kõks5Sulev Kõks6Francois H. van der Westhuizen7Joanna L. Elson8Joanna L. Elson9Soraya Bardien10Soraya Bardien11Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaSouth African Medical Research Council, Stellenbosch University Genomics of Brain Disorders Research Unit, Stellenbosch University, Cape Town, South AfricaPerron Institute for Neurological and Translational Science, Nedlands, WA, AustraliaCentre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, WA, AustraliaInstitute of Clinical Sciences, University of Birmingham, Birmingham, United KingdomPerron Institute for Neurological and Translational Science, Nedlands, WA, AustraliaCentre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, WA, AustraliaHuman Metabolomics, North-West University, Potchefstroom, South AfricaHuman Metabolomics, North-West University, Potchefstroom, South AfricaInstitute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United KingdomDivision of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaSouth African Medical Research Council, Stellenbosch University Genomics of Brain Disorders Research Unit, Stellenbosch University, Cape Town, South AfricaMitochondrial DNA (mtDNA), a potential source of mitochondrial dysfunction, has been implicated in Parkinson’s disease (PD). However, many previous studies investigating associations between mtDNA population variation and PD reported inconsistent or contradictory findings. Here, we investigated an alternative hypothesis to determine whether mtDNA variation could play a significant role in PD risk. Emerging evidence suggests that haplogroup-defining mtDNA variants may have pathogenic potential if they occur “out-of-place” on a different maternal lineage. We hypothesized that the mtDNA of PD cases would be enriched for out-of-place variation in genes encoding components of the oxidative phosphorylation complexes. We tested this hypothesis with a unique dataset comprising whole mitochondrial genomes of 70 African ancestry PD cases, two African ancestry control groups (n = 78 and n = 53) and a replication group of 281 European ancestry PD cases and 140 controls from the Parkinson’s Progression Markers Initiative cohort. Significantly more African ancestry PD cases had out-of-place variants than controls from the second control group (P < 0.0125), although this association was not observed in the first control group nor the replication group. As the first mtDNA study to include African ancestry PD cases and to explore out-of-place variation in a PD context, we found evidence that such variation might be significant in this context, thereby warranting further replication in larger cohorts.https://www.frontiersin.org/articles/10.3389/fnagi.2022.921412/fullParkinsion’s diseaseAfrican ancestrymitochondrial DNAmtDNAPPMI cohortout-of-place variation |
| spellingShingle | Amica C. Müller-Nedebock Amica C. Müller-Nedebock Abigail L. Pfaff Abigail L. Pfaff Ilse S. Pienaar Sulev Kõks Sulev Kõks Francois H. van der Westhuizen Joanna L. Elson Joanna L. Elson Soraya Bardien Soraya Bardien Mitochondrial DNA variation in Parkinson’s disease: Analysis of “out-of-place” population variants as a risk factor Frontiers in Aging Neuroscience Parkinsion’s disease African ancestry mitochondrial DNA mtDNA PPMI cohort out-of-place variation |
| title | Mitochondrial DNA variation in Parkinson’s disease: Analysis of “out-of-place” population variants as a risk factor |
| title_full | Mitochondrial DNA variation in Parkinson’s disease: Analysis of “out-of-place” population variants as a risk factor |
| title_fullStr | Mitochondrial DNA variation in Parkinson’s disease: Analysis of “out-of-place” population variants as a risk factor |
| title_full_unstemmed | Mitochondrial DNA variation in Parkinson’s disease: Analysis of “out-of-place” population variants as a risk factor |
| title_short | Mitochondrial DNA variation in Parkinson’s disease: Analysis of “out-of-place” population variants as a risk factor |
| title_sort | mitochondrial dna variation in parkinson s disease analysis of out of place population variants as a risk factor |
| topic | Parkinsion’s disease African ancestry mitochondrial DNA mtDNA PPMI cohort out-of-place variation |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.921412/full |
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