Toggle Main Menu Toggle Search

Open Access padlockePrints

Mitochondrial DNA population variation is not associated with Alzheimer's in the Japanese population: A consistent finding across global populations

Lookup NU author(s): Dr Jannetta Steyn, Dr Ilse Pienaar, Dr Joanna Elson



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


Several mitochondrial DNA (mtDNA) haplogroup association studies have suggested that common mtDNA variants are associated with multifactorial diseases, including Alzheimer's disease (AD). However, such studies have also produced conflicting results. A new mtDNA association model, the 'variant load model' (VLM), has been applied to multiple disease phenotypes. Application of the VLM in a 2017 study failed to find different variant loads in AD patients compared to controls, in two cohorts of European origin. The study also suggested a lower variant load in healthy elderly individuals, but could offer no replicate cohort to support this observation. Here, the VLM is applied to Japanese mtDNA sequences; in doing so, we explored the role of mtDNA variation in AD and ageing in a different global population. Consistent with the previous findings using the VLM in two populations of European origin, we found no evidence for an association between rarer, non-haplogroup associated variation and the development of AD. However, the result in the context of ageing that suggested those with fewer mildly deleterious mutations might undergo healthier ageing, was not replicated. In contrast to our previous study, our present results suggest that those living to advanced old age may harbour more mildly deleterious mtDNA variations. Importantly our analysis showed this finding is not primarily being driven by many rare population variants dispersed across the mtDNA, but by a few more frequent variants with high MutPred scores. It is suggested the variants in question do not exert a mildly deleterious effect in their most frequent haplogroup context.

Publication metadata

Author(s): Wong J, Steyn JS, Pienaar IS, Elson JL

Publication type: Article

Publication status: Published

Journal: PLoS ONE

Year: 2022

Volume: 17

Issue: 10

Online publication date: 20/10/2022

Acceptance date: 02/10/2022

Date deposited: 02/11/2022

ISSN (electronic): 1932-6203

Publisher: Public Library of Science


DOI: 10.1371/journal.pone.0276169

PubMed id: 36264923


Altmetrics provided by Altmetric