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The Effect of Alzheimer’s Disease-Associated Genetic Variants on Longevity
Human longevity is influenced by the genetic risk of age-related diseases. As Alzheimer’s disease (AD) represents a common condition at old age, an interplay between genetic factors affecting AD and longevity is expected. We explored this interplay by studying the prevalence of AD-associated single-...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724252/ https://www.ncbi.nlm.nih.gov/pubmed/34992629 http://dx.doi.org/10.3389/fgene.2021.748781 |
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author | Tesi, Niccolò Hulsman, Marc van der Lee, Sven J. Jansen, Iris E. Stringa, Najada van Schoor, Natasja M. Scheltens, Philip van der Flier, Wiesje M. Huisman, Martijn Reinders, Marcel J. T. Holstege, Henne |
author_facet | Tesi, Niccolò Hulsman, Marc van der Lee, Sven J. Jansen, Iris E. Stringa, Najada van Schoor, Natasja M. Scheltens, Philip van der Flier, Wiesje M. Huisman, Martijn Reinders, Marcel J. T. Holstege, Henne |
author_sort | Tesi, Niccolò |
collection | PubMed |
description | Human longevity is influenced by the genetic risk of age-related diseases. As Alzheimer’s disease (AD) represents a common condition at old age, an interplay between genetic factors affecting AD and longevity is expected. We explored this interplay by studying the prevalence of AD-associated single-nucleotide-polymorphisms (SNPs) in cognitively healthy centenarians, and replicated findings in a parental-longevity GWAS. We found that 28/38 SNPs that increased AD-risk also associated with lower odds of longevity. For each SNP, we express the imbalance between AD- and longevity-risk as an effect-size distribution. Based on these distributions, we grouped the SNPs in three groups: 17 SNPs increased AD-risk more than they decreased longevity-risk, and were enriched for β-amyloid metabolism and immune signaling; 11 variants reported a larger longevity-effect compared to their AD-effect, were enriched for endocytosis/immune-signaling, and were previously associated with other age-related diseases. Unexpectedly, 10 variants associated with an increased risk of AD and higher odds of longevity. Altogether, we show that different AD-associated SNPs have different effects on longevity, including SNPs that may confer general neuro-protective functions against AD and other age-related diseases. |
format | Online Article Text |
id | pubmed-8724252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87242522022-01-05 The Effect of Alzheimer’s Disease-Associated Genetic Variants on Longevity Tesi, Niccolò Hulsman, Marc van der Lee, Sven J. Jansen, Iris E. Stringa, Najada van Schoor, Natasja M. Scheltens, Philip van der Flier, Wiesje M. Huisman, Martijn Reinders, Marcel J. T. Holstege, Henne Front Genet Genetics Human longevity is influenced by the genetic risk of age-related diseases. As Alzheimer’s disease (AD) represents a common condition at old age, an interplay between genetic factors affecting AD and longevity is expected. We explored this interplay by studying the prevalence of AD-associated single-nucleotide-polymorphisms (SNPs) in cognitively healthy centenarians, and replicated findings in a parental-longevity GWAS. We found that 28/38 SNPs that increased AD-risk also associated with lower odds of longevity. For each SNP, we express the imbalance between AD- and longevity-risk as an effect-size distribution. Based on these distributions, we grouped the SNPs in three groups: 17 SNPs increased AD-risk more than they decreased longevity-risk, and were enriched for β-amyloid metabolism and immune signaling; 11 variants reported a larger longevity-effect compared to their AD-effect, were enriched for endocytosis/immune-signaling, and were previously associated with other age-related diseases. Unexpectedly, 10 variants associated with an increased risk of AD and higher odds of longevity. Altogether, we show that different AD-associated SNPs have different effects on longevity, including SNPs that may confer general neuro-protective functions against AD and other age-related diseases. Frontiers Media S.A. 2021-12-21 /pmc/articles/PMC8724252/ /pubmed/34992629 http://dx.doi.org/10.3389/fgene.2021.748781 Text en Copyright © 2021 Tesi, Hulsman, van der Lee, Jansen, Stringa, van Schoor, Scheltens, van der Flier, Huisman, Reinders and Holstege. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Tesi, Niccolò Hulsman, Marc van der Lee, Sven J. Jansen, Iris E. Stringa, Najada van Schoor, Natasja M. Scheltens, Philip van der Flier, Wiesje M. Huisman, Martijn Reinders, Marcel J. T. Holstege, Henne The Effect of Alzheimer’s Disease-Associated Genetic Variants on Longevity |
title | The Effect of Alzheimer’s Disease-Associated Genetic Variants on Longevity |
title_full | The Effect of Alzheimer’s Disease-Associated Genetic Variants on Longevity |
title_fullStr | The Effect of Alzheimer’s Disease-Associated Genetic Variants on Longevity |
title_full_unstemmed | The Effect of Alzheimer’s Disease-Associated Genetic Variants on Longevity |
title_short | The Effect of Alzheimer’s Disease-Associated Genetic Variants on Longevity |
title_sort | effect of alzheimer’s disease-associated genetic variants on longevity |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724252/ https://www.ncbi.nlm.nih.gov/pubmed/34992629 http://dx.doi.org/10.3389/fgene.2021.748781 |
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