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Polygenic Risk Score of Longevity Predicts Longer Survival Across an Age Continuum
Studying the genome of centenarians may give insights into the molecular mechanisms underlying extreme human longevity and the escape of age-related diseases. Here, we set out to construct polygenic risk scores (PRSs) for longevity and to investigate the functions of longevity-associated variants. U...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087277/ https://www.ncbi.nlm.nih.gov/pubmed/33216869 http://dx.doi.org/10.1093/gerona/glaa289 |
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author | Tesi, Niccolo’ van der Lee, Sven J Hulsman, Marc 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, Niccolo’ van der Lee, Sven J Hulsman, Marc 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, Niccolo’ |
collection | PubMed |
description | Studying the genome of centenarians may give insights into the molecular mechanisms underlying extreme human longevity and the escape of age-related diseases. Here, we set out to construct polygenic risk scores (PRSs) for longevity and to investigate the functions of longevity-associated variants. Using a cohort of centenarians with maintained cognitive health (N = 343), a population-matched cohort of older adults from 5 cohorts (N = 2905), and summary statistics data from genome-wide association studies on parental longevity, we constructed a PRS including 330 variants that significantly discriminated between centenarians and older adults. This PRS was also associated with longer survival in an independent sample of younger individuals (p = .02), leading up to a 4-year difference in survival based on common genetic factors only. We show that this PRS was, in part, able to compensate for the deleterious effect of the APOE-ε4 allele. Using an integrative framework, we annotated the 330 variants included in this PRS by the genes they associate with. We find that they are enriched with genes associated with cellular differentiation, developmental processes, and cellular response to stress. Together, our results indicate that an extended human life span is, in part, the result of a constellation of variants each exerting small advantageous effects on aging-related biological mechanisms that maintain overall health and decrease the risk of age-related diseases. |
format | Online Article Text |
id | pubmed-8087277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-80872772021-05-05 Polygenic Risk Score of Longevity Predicts Longer Survival Across an Age Continuum Tesi, Niccolo’ van der Lee, Sven J Hulsman, Marc Jansen, Iris E Stringa, Najada van Schoor, Natasja M Scheltens, Philip van der Flier, Wiesje M Huisman, Martijn Reinders, Marcel J T Holstege, Henne J Gerontol A Biol Sci Med Sci THE JOURNAL OF GERONTOLOGY: Biological Sciences Studying the genome of centenarians may give insights into the molecular mechanisms underlying extreme human longevity and the escape of age-related diseases. Here, we set out to construct polygenic risk scores (PRSs) for longevity and to investigate the functions of longevity-associated variants. Using a cohort of centenarians with maintained cognitive health (N = 343), a population-matched cohort of older adults from 5 cohorts (N = 2905), and summary statistics data from genome-wide association studies on parental longevity, we constructed a PRS including 330 variants that significantly discriminated between centenarians and older adults. This PRS was also associated with longer survival in an independent sample of younger individuals (p = .02), leading up to a 4-year difference in survival based on common genetic factors only. We show that this PRS was, in part, able to compensate for the deleterious effect of the APOE-ε4 allele. Using an integrative framework, we annotated the 330 variants included in this PRS by the genes they associate with. We find that they are enriched with genes associated with cellular differentiation, developmental processes, and cellular response to stress. Together, our results indicate that an extended human life span is, in part, the result of a constellation of variants each exerting small advantageous effects on aging-related biological mechanisms that maintain overall health and decrease the risk of age-related diseases. Oxford University Press 2020-11-20 /pmc/articles/PMC8087277/ /pubmed/33216869 http://dx.doi.org/10.1093/gerona/glaa289 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | THE JOURNAL OF GERONTOLOGY: Biological Sciences Tesi, Niccolo’ van der Lee, Sven J Hulsman, Marc Jansen, Iris E Stringa, Najada van Schoor, Natasja M Scheltens, Philip van der Flier, Wiesje M Huisman, Martijn Reinders, Marcel J T Holstege, Henne Polygenic Risk Score of Longevity Predicts Longer Survival Across an Age Continuum |
title | Polygenic Risk Score of Longevity Predicts Longer Survival Across an Age Continuum |
title_full | Polygenic Risk Score of Longevity Predicts Longer Survival Across an Age Continuum |
title_fullStr | Polygenic Risk Score of Longevity Predicts Longer Survival Across an Age Continuum |
title_full_unstemmed | Polygenic Risk Score of Longevity Predicts Longer Survival Across an Age Continuum |
title_short | Polygenic Risk Score of Longevity Predicts Longer Survival Across an Age Continuum |
title_sort | polygenic risk score of longevity predicts longer survival across an age continuum |
topic | THE JOURNAL OF GERONTOLOGY: Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087277/ https://www.ncbi.nlm.nih.gov/pubmed/33216869 http://dx.doi.org/10.1093/gerona/glaa289 |
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