Genetically predicted telomere length and its relationship with neurodegenerative diseases and life expectancy

Telomere length (TL) is a biomarker of biological aging. Shorter telomeres have been associated with mortality and increased rates of age-related diseases. However, observational studies are unable to conclude whether TL is causally associated with those outcomes. Mendelian randomization (MR) was de...

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Autores: Rodríguez Fernández, Blanca, Gispert, Juan Domingo, Guigo, Roderic, Navarro, Arcadi, Vilor Tejedor, Natalia, Crous Bou, Marta
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/205337
Acceso en línea:https://hdl.handle.net/2445/205337
Access Level:acceso abierto
Palabra clave:Malalties neurodegeneratives
Telòmer
Neurodegenerative Diseases
Telomere
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spelling Genetically predicted telomere length and its relationship with neurodegenerative diseases and life expectancyRodríguez Fernández, BlancaGispert, Juan DomingoGuigo, RodericNavarro, ArcadiVilor Tejedor, NataliaCrous Bou, MartaMalalties neurodegenerativesTelòmerNeurodegenerative DiseasesTelomereTelomere length (TL) is a biomarker of biological aging. Shorter telomeres have been associated with mortality and increased rates of age-related diseases. However, observational studies are unable to conclude whether TL is causally associated with those outcomes. Mendelian randomization (MR) was developed for assessing causality using genetic variants in epidemiological research. The objective of this study was to test the potential causal role of TL in neurodegenerative disorders and life expectancy through MR analysis. Summary level data were extracted from the most recent genome-wide association studies for TL, Alzheimer's disease (AD), Parkinson's disease, Frontotemporal dementia, Amyotrophic Lateral Sclerosis, Progressive Supranuclear Palsy and life expectancy. MR estimates revealed that longer telomeres inferred a protective effect on risk of AD (OR = 0.964; adjusted p-value = 0.039). Moreover, longer telomeres were significantly associated with increased life expectancy (beta(IVW) = 0.011; adjusted p-value = 0.039). Sensitivity analyses suggested evidence for directional pleiotropy in AD analyses. Our results showed that genetically predicted longer TL may increase life expectancy and play a protective causal effect on AD. We did not observe significant causal relationships between longer TL and other neurodegenerative diseases. This suggests that the involvement of TL on specific biological mechanisms might differ between AD and life expectancy, with respect to that in other neurodegenerative diseases. Moreover, the presence of pleiotropy may reflect the complex interplay between TL homeostasis and AD pathophysiology. Further observational studies are needed to confirm these results. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Elsevier BV2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/205337Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.csbj.2022.08.006Computational and Structural Biotechnology Journal, 2022, vol. 20, p. 4251-4256https://doi.org/10.1016/j.csbj.2022.08.006cc by-nc-nd (c) Rodríguez Fernández, Blanca et al., 2022http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2053372026-05-27T06:46:51Z
dc.title.none.fl_str_mv Genetically predicted telomere length and its relationship with neurodegenerative diseases and life expectancy
title Genetically predicted telomere length and its relationship with neurodegenerative diseases and life expectancy
spellingShingle Genetically predicted telomere length and its relationship with neurodegenerative diseases and life expectancy
Rodríguez Fernández, Blanca
Malalties neurodegeneratives
Telòmer
Neurodegenerative Diseases
Telomere
title_short Genetically predicted telomere length and its relationship with neurodegenerative diseases and life expectancy
title_full Genetically predicted telomere length and its relationship with neurodegenerative diseases and life expectancy
title_fullStr Genetically predicted telomere length and its relationship with neurodegenerative diseases and life expectancy
title_full_unstemmed Genetically predicted telomere length and its relationship with neurodegenerative diseases and life expectancy
title_sort Genetically predicted telomere length and its relationship with neurodegenerative diseases and life expectancy
dc.creator.none.fl_str_mv Rodríguez Fernández, Blanca
Gispert, Juan Domingo
Guigo, Roderic
Navarro, Arcadi
Vilor Tejedor, Natalia
Crous Bou, Marta
author Rodríguez Fernández, Blanca
author_facet Rodríguez Fernández, Blanca
Gispert, Juan Domingo
Guigo, Roderic
Navarro, Arcadi
Vilor Tejedor, Natalia
Crous Bou, Marta
author_role author
author2 Gispert, Juan Domingo
Guigo, Roderic
Navarro, Arcadi
Vilor Tejedor, Natalia
Crous Bou, Marta
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Malalties neurodegeneratives
Telòmer
Neurodegenerative Diseases
Telomere
topic Malalties neurodegeneratives
Telòmer
Neurodegenerative Diseases
Telomere
description Telomere length (TL) is a biomarker of biological aging. Shorter telomeres have been associated with mortality and increased rates of age-related diseases. However, observational studies are unable to conclude whether TL is causally associated with those outcomes. Mendelian randomization (MR) was developed for assessing causality using genetic variants in epidemiological research. The objective of this study was to test the potential causal role of TL in neurodegenerative disorders and life expectancy through MR analysis. Summary level data were extracted from the most recent genome-wide association studies for TL, Alzheimer's disease (AD), Parkinson's disease, Frontotemporal dementia, Amyotrophic Lateral Sclerosis, Progressive Supranuclear Palsy and life expectancy. MR estimates revealed that longer telomeres inferred a protective effect on risk of AD (OR = 0.964; adjusted p-value = 0.039). Moreover, longer telomeres were significantly associated with increased life expectancy (beta(IVW) = 0.011; adjusted p-value = 0.039). Sensitivity analyses suggested evidence for directional pleiotropy in AD analyses. Our results showed that genetically predicted longer TL may increase life expectancy and play a protective causal effect on AD. We did not observe significant causal relationships between longer TL and other neurodegenerative diseases. This suggests that the involvement of TL on specific biological mechanisms might differ between AD and life expectancy, with respect to that in other neurodegenerative diseases. Moreover, the presence of pleiotropy may reflect the complex interplay between TL homeostasis and AD pathophysiology. Further observational studies are needed to confirm these results. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/205337
url https://hdl.handle.net/2445/205337
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.csbj.2022.08.006
Computational and Structural Biotechnology Journal, 2022, vol. 20, p. 4251-4256
https://doi.org/10.1016/j.csbj.2022.08.006
dc.rights.none.fl_str_mv cc by-nc-nd (c) Rodríguez Fernández, Blanca et al., 2022
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Rodríguez Fernández, Blanca et al., 2022
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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