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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-...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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