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

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• dc.contributor.author Rodríguez-Fernández, Blanca
• dc.contributor.author Gispert López, Juan Domingo
• dc.contributor.author Guigó Serra, Roderic
• dc.contributor.author Navarro i Cuartiellas, Arcadi, 1969-
• dc.contributor.author Vilor Tejedor, Natàlia, 1988-
• dc.contributor.author Crous-Bou, Marta
• dc.date.accessioned 2022-09-13T06:23:12Z
• dc.date.available 2022-09-13T06:23:12Z
• dc.date.issued 2022
• dc.description.abstract 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 (βIVW = 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Rodríguez-Fernández B, Gispert JD, Guigo R, Navarro A, Vilor-Tejedor N, Crous-Bou M. Genetically predicted telomere length and its relationship with neurodegenerative diseases and life expectancy. Comput Struct Biotechnol J. 2022 Aug 6;20:4251-6. DOI: 10.1016/j.csbj.2022.08.006
• dc.identifier.doi http://dx.doi.org/10.1016/j.csbj.2022.08.006
• dc.identifier.issn 2001-0370
• dc.identifier.uri http://hdl.handle.net/10230/54048
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Comput Struct Biotechnol J. 2022 Aug 6;20:4251-6
• dc.rights © 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/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword AD, Alzheimer’s disease
• dc.subject.keyword ALS, Amyotrophic lateral sclerosis
• dc.subject.keyword Alzheimer’s disease
• dc.subject.keyword CI, Confidence Interval
• dc.subject.keyword FTD, Frontotemporal dementia
• dc.subject.keyword GWAS, Genome-wide association study
• dc.subject.keyword IV, Instrumental Variable
• dc.subject.keyword IVW, Inverse-Variance Weighted
• dc.subject.keyword LRRC34, Leucine Rich Repeat Containing 34
• dc.subject.keyword Life expectancy
• dc.subject.keyword MR, Mendelian Randomization
• dc.subject.keyword MR-PRESSO, MR-Pleiotropy RESidual Sum and Outlier
• dc.subject.keyword Mendelian randomization
• dc.subject.keyword Neurodegenerative diseases
• dc.subject.keyword OR, Odds ratio
• dc.subject.keyword PD, Parkinson’s disease
• dc.subject.keyword PSP, Progressive Supranuclear Palsy
• dc.subject.keyword SE, Standard Error
• dc.subject.keyword SNP, Single Nucleotide Polymorphism
• dc.subject.keyword TL, Telomere length
• dc.subject.keyword Telomere length
• dc.title Genetically predicted telomere length and its relationship with neurodegenerative diseases and life expectancy
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion