Dataset Information

Genetically predicted telomere length and Alzheimer's disease endophenotypes: a Mendelian randomization study.

ABSTRACT: Telomere length (TL) is associated with biological aging, consequently influencing the risk of age-related diseases such as Alzheimer's disease (AD). We aimed to evaluate the potential causal role of TL in AD endophenotypes (i.e., cognitive performance, N = 2233; brain age and AD-related signatures, N = 1134; and cerebrospinal fluid biomarkers (CSF) of AD and neurodegeneration, N = 304) through a Mendelian randomization (MR) analysis. Our analysis was conducted in the context of the ALFA (ALzheimer and FAmilies) study, a population of cognitively healthy individuals at risk of AD. A total of 20 single nucleotide polymorphisms associated with TL were used to determine the effect of TL on AD endophenotypes. Analyses were adjusted by age, sex, and years of education. Stratified analyses by APOE-ɛ4 status and polygenic risk score of AD were conducted. MR analysis revealed significant associations between genetically predicted longer TL and lower levels of CSF Aβ and higher levels of CSF NfL only in APOE-ɛ4 non-carriers. Moreover, inheriting longer TL was associated with greater cortical thickness in age and AD-related brain signatures and lower levels of CSF p-tau among individuals at a high genetic predisposition to AD. Further observational analyses are warranted to better understand these associations.

SUBMITTER: Rodriguez-Fernandez B

PROVIDER: S-EPMC9641781 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetically predicted telomere length and Alzheimer's disease endophenotypes: a Mendelian randomization study.

Rodríguez-Fernández Blanca B Vilor-Tejedor Natalia N Arenaza-Urquijo Eider M EM Sánchez-Benavides Gonzalo G Suárez-Calvet Marc M Operto Grégory G Minguillón Carolina C Fauria Karine K Kollmorgen Gwendlyn G Suridjan Ivonne I de Moura Manuel Castro MC Piñeyro David D Esteller Manel M Blennow Kaj K Zetterberg Henrik H De Vivo Immaculata I Molinuevo José Luis JL Navarro Arcadi A Gispert Juan Domingo JD Sala-Vila Aleix A Crous-Bou Marta M

Alzheimer's research & therapy 20221107 1

Telomere length (TL) is associated with biological aging, consequently influencing the risk of age-related diseases such as Alzheimer's disease (AD). We aimed to evaluate the potential causal role of TL in AD endophenotypes (i.e., cognitive performance, N = 2233; brain age and AD-related signatures, N = 1134; and cerebrospinal fluid biomarkers (CSF) of AD and neurodegeneration, N = 304) through a Mendelian randomization (MR) analysis. Our analysis was conducted in the context of the ALFA (ALzhei ...[more]

PMID: 36345036

Similar Datasets

Project description:BackgroundTelomere length (TL) has been regarded as a biomarker of aging, and TL shortening is associated with numerous chronic illnesses. The mounting evidence has shown that inflammatory cytokines are involved in maintaining or shortening TL, the causality of cytokines with TL remains unknown. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to estimate the underlying correlations of circulating inflammatory cytokines with TL.MethodsGenetic instrumental variables for inflammatory cytokines were identified through a genome-wide association study (GWAS) involving 8,293 European individuals. Summary statistics of TL were derived from a UK Bio-bank cohort comprising 472,174 samples of individuals with European descent. We employed the inverse-variance weighted (IVW) approach as our main analysis, and to ensure the reliability of our findings, we also conducted additional analyses including the weighted median, MR-Egger, MR pleiotropy residual sum and outlier test, and weighted model. Lastly, the reverse MR analyses were performed to estimate the likelihood of inverse causality between TL and the cytokines identified in the forward MR analysis. Cochran's Q test were employed to quantify the degree of heterogeneity.ResultsAfter applying Bonferroni correction, a higher circulating level of Interleukin-7 (IL-7) was suggestively associated with TL maintaining (OR:1.01, 95%CI:1.00-1.02, P=0.032 by IVW method). The study also revealed suggestive evidence indicating the involvement of Interleukin-2 receptor, alpha subunit (IL-2Rα) level was negatively associated with TL maintaining (OR:0.98, 95%CI:0.96-1.00, P=0.045 by IVW method), and the weighted median approach was consistent (OR:0.99, 95%CI:0.97-1.00, P=0.035). According to the findings of reverse MR analysis, no significant causal relationship between TL and cytokines was explored. Our analysis did not reveal any substantial heterogeneity in the Single nucleotide polymorphisms or horizontal pleiotropy.ConclusionsOur MR analysis yielded suggestive evidence supporting the causality between circulating IL-7 and IL-2Rα and telomere length, necessitating further investigations to elucidate the mechanisms by which these inflammatory cytokines may impact the progression of telomeres.

Dataset Information

Genetically predicted telomere length and Alzheimer's disease endophenotypes: a Mendelian randomization study.

Publications

Genetically predicted telomere length and Alzheimer's disease endophenotypes: a Mendelian randomization study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets