Causal association between serum 25-hydroxyvitamin D levels and epilepsy: A two-sample bidirectional mendelian randomization study.

Objective: The study aimed to investigate the causal relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and epilepsy using Mendelian randomization (MR), thereby addressing confounding and reverse causality issues in observational studies.

Methods: We employed a two-sample bidirectional MR design utilizing summary-level data from the IEU OpenGWAS project. Serum 25(OH)D levels were analyzed using the publicly available dataset ebi-a-GCST90000618, which included 496,946 European samples and 68,960,93 SNPs. Data on epilepsy were obtained from ebi-a-GCST90018840, comprising 458,310 samples, including 4,382 epilepsy patients and 453,928 controls. To identify instrumental variables (IVs), we applied a significance threshold of P < 5e-8 for serum 25(OH)D levels as the exposure and P < 5e-6 for epilepsy as the exposure. IVs were required to demonstrate an r² < 0.001 linkage disequilibrium and an F-statistic greater than 10. The MR analysis utilized five methods: inverse variance weighted (IVW), weighted median, MR-Egger, weighted mode, and simple mode, assessing causal relationships between serum 25(OH)D levels and epilepsy. Robustness checks included heterogeneity tests, leave-one-out sensitivity analyses, and assessments for horizontal pleiotropy.

Results: Both directions of the MR analysis revealed no genetic correlation between serum 25(OH)D levels and epilepsy.

Conclusion: Our findings, supported by robust IV screening and consistent results across multiple MR methods, indicate a lack of causal relationship between serum 25(OH)D levels and epilepsy. These results suggest that while vitamin D plays a role in the nervous system, its relationship to epilepsy may not be direct, thus highlighting the need for further investigation in future studies.