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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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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. |
format | Online Article Text |
id | pubmed-9584534 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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