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Mitonuclear interactions influence Alzheimer’s disease risk
We examined the associations between mitochondrial DNA haplogroups (MT-hgs; mitochondrial haplotype groups defined by a specific combination of single nucleotide polymorphisms labeled as letters running from A to Z) and their interactions with a polygenic risk score composed of nuclear-encoded mitoc...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205324/ https://www.ncbi.nlm.nih.gov/pubmed/31784277 http://dx.doi.org/10.1016/j.neurobiolaging.2019.09.007 |
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author | Andrews, Shea J. Fulton-Howard, Brian Patterson, Christopher McFall, G Peggy Gross, Alden Michaelis, Elias K. Goate, Alison Swerdlow, Russell H. Pa, Judy |
author_facet | Andrews, Shea J. Fulton-Howard, Brian Patterson, Christopher McFall, G Peggy Gross, Alden Michaelis, Elias K. Goate, Alison Swerdlow, Russell H. Pa, Judy |
author_sort | Andrews, Shea J. |
collection | PubMed |
description | We examined the associations between mitochondrial DNA haplogroups (MT-hgs; mitochondrial haplotype groups defined by a specific combination of single nucleotide polymorphisms labeled as letters running from A to Z) and their interactions with a polygenic risk score composed of nuclear-encoded mitochondrial genes (nMT-PRS) with risk of dementia and age of onset (AOO) of dementia. MT-hg K (Odds ratio [OR]: 2.03 [95% CI: 1.04, 3.97]) and a 1 SD larger nMT-PRS (OR: 2.2 [95% CI: 1.68, 2.86]) were associated with elevated odds of dementia. Significant antagonistic interactions between the nMT-PRS and MT-hg K (OR: 0.45 [95% CI: 0.22, 0.9]) and MT-hg T (OR: 0.22 [95% CI: 0.1, 0.49]) were observed. Individual MT-hgs were not associated with AOO; however, a significant antagonistic interactions was observed between the nMT-PRS and MT-hg T (Hazard ratio: 0.62 [95% CI: 0.42, 0.91]) and a synergistic interaction between the nMT-PRS and MT-hg V (Hazard ratio: 2.28 [95% CI: 1.19, 4.35]). These results suggest that MT-hgs influence dementia risk and that variants in the nuclear and mitochondrial genome interact to influence the AOO of dementia. |
format | Online Article Text |
id | pubmed-7205324 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-72053242021-03-01 Mitonuclear interactions influence Alzheimer’s disease risk Andrews, Shea J. Fulton-Howard, Brian Patterson, Christopher McFall, G Peggy Gross, Alden Michaelis, Elias K. Goate, Alison Swerdlow, Russell H. Pa, Judy Neurobiol Aging Article We examined the associations between mitochondrial DNA haplogroups (MT-hgs; mitochondrial haplotype groups defined by a specific combination of single nucleotide polymorphisms labeled as letters running from A to Z) and their interactions with a polygenic risk score composed of nuclear-encoded mitochondrial genes (nMT-PRS) with risk of dementia and age of onset (AOO) of dementia. MT-hg K (Odds ratio [OR]: 2.03 [95% CI: 1.04, 3.97]) and a 1 SD larger nMT-PRS (OR: 2.2 [95% CI: 1.68, 2.86]) were associated with elevated odds of dementia. Significant antagonistic interactions between the nMT-PRS and MT-hg K (OR: 0.45 [95% CI: 0.22, 0.9]) and MT-hg T (OR: 0.22 [95% CI: 0.1, 0.49]) were observed. Individual MT-hgs were not associated with AOO; however, a significant antagonistic interactions was observed between the nMT-PRS and MT-hg T (Hazard ratio: 0.62 [95% CI: 0.42, 0.91]) and a synergistic interaction between the nMT-PRS and MT-hg V (Hazard ratio: 2.28 [95% CI: 1.19, 4.35]). These results suggest that MT-hgs influence dementia risk and that variants in the nuclear and mitochondrial genome interact to influence the AOO of dementia. 2019-09-24 2020-03 /pmc/articles/PMC7205324/ /pubmed/31784277 http://dx.doi.org/10.1016/j.neurobiolaging.2019.09.007 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Andrews, Shea J. Fulton-Howard, Brian Patterson, Christopher McFall, G Peggy Gross, Alden Michaelis, Elias K. Goate, Alison Swerdlow, Russell H. Pa, Judy Mitonuclear interactions influence Alzheimer’s disease risk |
title | Mitonuclear interactions influence Alzheimer’s disease risk |
title_full | Mitonuclear interactions influence Alzheimer’s disease risk |
title_fullStr | Mitonuclear interactions influence Alzheimer’s disease risk |
title_full_unstemmed | Mitonuclear interactions influence Alzheimer’s disease risk |
title_short | Mitonuclear interactions influence Alzheimer’s disease risk |
title_sort | mitonuclear interactions influence alzheimer’s disease risk |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205324/ https://www.ncbi.nlm.nih.gov/pubmed/31784277 http://dx.doi.org/10.1016/j.neurobiolaging.2019.09.007 |
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