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

Blanca Rodríguez-Fernández, Juan Domingo Gispert, Roderic Guigo, Arcadi Navarro, Natalia Vilor-Tejedor*, Marta Crous-Bou*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)4251-4256
Number of pages6
JournalComputational and Structural Biotechnology Journal
Publication statusPublished - Jan 2022

Bibliographical note

Funding Information:
This project has received funding from the Alzheimer’s Association (Grant AARG-19-618265). JDG is supported by the Spanish Ministry of Science and Innovation (RYC-2013-13054) Ministry of Science and Innovation– Spanish State Research Agency. NV-T is funded by a postdoctoral grant, Juan de la Cierva Programme (IJC2020-043216-I). All CRG authors acknowledge the support of the Spanish Ministry of Science, Innovation and Universities to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme / Generalitat de Catalunya.

Publisher Copyright:
© 2022 The Author(s)


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