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...
| Autores: | , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universitat Pompeu Fabra |
| Repositorio: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/54048 |
| Acceso en línea: | http://hdl.handle.net/10230/54048 http://dx.doi.org/10.1016/j.csbj.2022.08.006 |
| Access Level: | acceso abierto |
| Palabra clave: | AD, Alzheimer’s disease ALS, Amyotrophic lateral sclerosis Alzheimer’s disease CI, Confidence Interval FTD, Frontotemporal dementia GWAS, Genome-wide association study IV, Instrumental Variable IVW, Inverse-Variance Weighted LRRC34, Leucine Rich Repeat Containing 34 Life expectancy MR, Mendelian Randomization MR-PRESSO, MR-Pleiotropy RESidual Sum and Outlier Mendelian randomization Neurodegenerative diseases OR, Odds ratio PD, Parkinson’s disease PSP, Progressive Supranuclear Palsy SE, Standard Error SNP, Single Nucleotide Polymorphism TL, Telomere length Telomere length |
| Sumario: | 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. |
|---|