Murdoch University Research Repository

Welcome to the Murdoch University Research Repository

The Murdoch University Research Repository is an open access digital collection of research
created by Murdoch University staff, researchers and postgraduate students.

Learn more

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

Müller-Nedebock, A.C., Pfaff, A.L.ORCID: 0000-0002-2231-9800, Pienaar, I.S., Kõks, S., van der Westhuizen, F.H., Elson, J.L. and Bardien, S. (2022) Mitochondrial DNA variation in Parkinson’s disease: Analysis of “out-of-place” population variants as a risk factor. Frontiers in Aging Neuroscience, 14 . Art. 921412.

PDF - Published Version
Download (2MB) | Preview
Free to read:
*No subscription required


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.

Item Type: Journal Article
Murdoch Affiliation(s): Centre for Molecular Medicine and Innovative Therapeutics
Publisher: Frontiers
Copyright: © 2022 Müller-Nedebock et al.
United Nations SDGs: Goal 3: Good Health and Well-Being
Item Control Page Item Control Page


Downloads per month over past year