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

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 m...

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Autores principales: Wong, Johanna, Steyn, Jannetta S., Pienaar, Ilse S., Elson, Joanna L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584534/
https://www.ncbi.nlm.nih.gov/pubmed/36264923
http://dx.doi.org/10.1371/journal.pone.0276169
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author Wong, Johanna
Steyn, Jannetta S.
Pienaar, Ilse S.
Elson, Joanna L.
author_facet Wong, Johanna
Steyn, Jannetta S.
Pienaar, Ilse S.
Elson, Joanna L.
author_sort Wong, Johanna
collection PubMed
description 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.
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spelling pubmed-95845342022-10-21 Mitochondrial DNA population variation is not associated with Alzheimer’s in the Japanese population: A consistent finding across global populations Wong, Johanna Steyn, Jannetta S. Pienaar, Ilse S. Elson, Joanna L. PLoS One Research Article 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. Public Library of Science 2022-10-20 /pmc/articles/PMC9584534/ /pubmed/36264923 http://dx.doi.org/10.1371/journal.pone.0276169 Text en © 2022 Wong et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wong, Johanna
Steyn, Jannetta S.
Pienaar, Ilse S.
Elson, Joanna L.
Mitochondrial DNA population variation is not associated with Alzheimer’s in the Japanese population: A consistent finding across global populations
title Mitochondrial DNA population variation is not associated with Alzheimer’s in the Japanese population: A consistent finding across global populations
title_full Mitochondrial DNA population variation is not associated with Alzheimer’s in the Japanese population: A consistent finding across global populations
title_fullStr Mitochondrial DNA population variation is not associated with Alzheimer’s in the Japanese population: A consistent finding across global populations
title_full_unstemmed Mitochondrial DNA population variation is not associated with Alzheimer’s in the Japanese population: A consistent finding across global populations
title_short Mitochondrial DNA population variation is not associated with Alzheimer’s in the Japanese population: A consistent finding across global populations
title_sort mitochondrial dna population variation is not associated with alzheimer’s in the japanese population: a consistent finding across global populations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584534/
https://www.ncbi.nlm.nih.gov/pubmed/36264923
http://dx.doi.org/10.1371/journal.pone.0276169
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