Causal relationship between telomere length and epilepsy: A bidirectional Mendelian randomization study

Abstract

ObjectiveObservational studies have suggested a link between telomere length (TL) and epilepsy, but the direction of the effect and whether it is causal or not is still being debated. The objective of this study was to investigate the causal relationship between TL and epilepsy using Mendelian randomization (MR) analysis.MethodsWe performed a bidirectional two‐sample MR analysis using pooled statistics from genome‐wide association studies (GWAS) of TL and epilepsy. Additionally, we conducted a replication analysis using data from another GWAS study on epilepsy to validate our findings. The final results were analyzed using five MR methods, with the inverse‐variance weighted (IVW) method as the primary outcome. We applied methods such as radial MR, MR pleiotropy residual and outlier test and MR Steiger filters to exclude outliers. Sensitivity analyses were also conducted to assess heterogeneity and pleiotropy.ResultsOur analysis found no evidence of a causal relationship between epilepsy and TL (all P‐values > 0.05). The sensitivity analysis confirms the robustness of these results.SignificanceIn summary, our study contradicts existing observational reports by not finding any evidence to support a causal relationship between epilepsy and TL. Further research is necessary to determine the underlying mechanism behind the association observed in observational studies.

Correlation of telomere length in brain tissue with peripheral tissues in living human subjects

“…Few opportunities exist to obtain brain tissue from living subjects, so all samples in this study were collected from individuals with medically intractable epilepsy which is another limitation to generalizability. There are mixed results previously on the association of peripheral TL with epilepsy: one study found increased telomere shortening in patients with drug-resistant epilepsy (Miranda et al, 2020 ) and another study identified no TL differences in individuals with epilepsy (Luo et al, 2023 ). Another study shows that individuals with the rare disorder, Revesz syndrome, that often experience seizures display decreased ability of the shelterin complex to protect telomeres from shortening (Karremann et al, 2020 ).…”