Assessing the Causality Between Frailty and Epilepsy: Bidirectional 2-Sample Mendelian Randomization

Background Whereas a potential connection between epilepsy and frailty has been proposed in past research, the causal nature of this relationship requires additional study. Objective This research was designed to evaluate the bidirectional causality between epilepsy and frailty index (FI) through 2-sample Mendelian randomization (MR). Methods In this study, we applied genome-wide association studies to perform forward and reverse MR within a 2-sample context to explore the potential bidirectional causality between FI and epilepsy. The main analysis approach was the inverse variance weighted (IVW) used to assess the potential influence of causal relationships and to carry out sensitivity checks. Results MR analysis revealed a positive correlation between FI and the heightened risk of epilepsy [ORIVW = 1.2126, 95% confidence interval (CI): 1.0143–1.4497, P = 0.0343]. This correlation persists in MR analysis that excluded aberrant single nucleotide polymorphisms (ORIVW = 1.1862, 95% CI: 1.0236–1.3746, P = 0.0232). Reverse MR analysis corroborated a significant positive relationship between epilepsy and FI (ORIVW = 1.0896, 95% CI: 1.0242–1.1592, P = 0.0066), which was confirmed in subsequent replication analysis (ORIVW = 1.0975, 95% CI: 1.0532–1.1436, P = 9.69e-06). Sensitivity analysis further supported the hypothesis of a causal link between FI and epilepsy. Conclusion There is an evident bidirectional causal relationship between FI and epilepsy.