Müller-Nedebock, Amica C, Pfaff, Abigail L, Pienaar, Ilse S, Kõks, Sulev, van der Westhuizen, Francois H, Elson, Joanna L and Bardien, Soraya
(2022)
Mitochondrial DNA variation in Parkinson's disease: Analysis of "out-of-place" population variants as a risk factor.
Frontiers in aging neuroscience, 14.
p. 921412.
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Mitochondrial DNA variation in Parkinsons disease Analysis of out-of-place population variants as a risk factor.pdf - Published version Download (2MB) | Preview |
Abstract
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 (<i>n</i> = 78 and <i>n</i> = 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 (<i>P</i> < 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Parkinsion's disease, African ancestry, mitochondrial DNA, mtDNA, PPMI cohort, out-of-place variation, risk factor |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 05 Aug 2022 10:42 |
| Last Modified: | 18 Jan 2023 20:53 |
| DOI: | 10.3389/fnagi.2022.921412 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3160438 |
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