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Mitochondrial DNA variation in Parkinson’s disease: Analysis of “out-of-place” population variants as a risk factor

Lookup NU author(s): Dr Joanna Elson



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Copyright © 2022 Müller-Nedebock, Pfaff, Pienaar, Kõks, van der Westhuizen, Elson and Bardien.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.

Publication metadata

Author(s): Muller-Nedebock AC, Pfaff AL, Pienaar IS, Koks S, van der Westhuizen FH, Elson JL, Bardien S

Publication type: Article

Publication status: Published

Journal: Frontiers in Aging Neuroscience

Year: 2022

Volume: 14

Online publication date: 14/07/2022

Acceptance date: 30/06/2022

Date deposited: 12/08/2022

ISSN (electronic): 1663-4365

Publisher: Frontiers Media SA


DOI: 10.3389/fnagi.2022.921412


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Funder referenceFunder name
Michael J. Fox Foundation