Telomere Length and Lewy Body Dementia: Genetic Insights from Mendelian Randomization
Year: 2026
Type: article
Study design: Observational Study
Abstract: TELOMERE LENGTH AND LEWY BODY DEMENTIA: GENETIC INSIGHTS FROMMENDELIAN RANDOMIZATION IntroductionLewy body dementia (LBD) accounts for 20% of all dementia cases, and is marked bya progressive decline in cognitive, behavioural, and psychosocial functioning [1].Telomeres are the protective short sequences at the ends of chromosomes and theirshortening has been linked with geriatric disorders including LBD [2]. Observationalstudies investigating the links between telomere length and neurodegenerativeconditions including LBD, have presented with conflicting results [3-5]. Weinvestigated the potential causal relationship between genetically predicted telomerelength and LBD using Mendelian randomization (MR). MethodsWe performed a two-sample MR study to assess bidirectional causal effects betweentelomere length and LBD. Genome-wide significant SNPs (P < 5.0×10⁻⁸) wereextracted from GWAS summary statistics (telomere length: n = 438,351; LBD: n =6,618). Causal estimates were obtained using inverse-variance weighted (IVW), MREgger,weighted median, weighted mode, and simple mode approaches. Sensitivityanalyses included MR-Egger intercept, MR-PRESSO, Cochran’s Q test, Steiger test,and leave-one-out analysis. ResultsWe found no evidence of a causal effect of telomere length and LBD across allmethods of analysis. In the reverse direction, genetic liability to LBD on telomerelength demonstrated a modest causal effect: Inverse variance weighted odds ratio(OR) = 1.01; 95% CI: 1.00 – 1.02; P = 8.78×10⁻⁵; MR Egger OR = 1.01; 95% CI: 1.00– 1.03; P = 0.09; Weighted median OR = 1.01; 95% CI: 1.00 – 1.02; P = 0.0002; Simplemode OR = 1.01; 95% CI: 0.99 – 1.02; P = 0.13; Weighted mode OR = 1.01; 95% CI:1.00 – 1.02; P = 0.02. ConclusionOur findings provide little evidence for a causal effect of telomere length on LBD.Conversely, bidirectional analyses suggest that genetic liability to LBD may have amodest effect on increasing telomere length.
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7212299427
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