The causal effect of serum 25-hydroxyvitamin D levels on epilepsy: A two-sample Mendelian randomization study.

OBJECTIVE: Observational studies have shown an association between 25-hydroxyvitamin D (25(OH)D) and epilepsy, but it is unclear whether the association is causal. Therefore, we applied Mendelian randomization (MR) analysis to determine the causal relationship between serum 25(OH)D levels and epilepsy.

METHODS: We conducted a two-sample Mendelian randomization (TSMR) study to investigate the association between serum 25(OH)D levels and epilepsy using pooled statistics from genome-wide association studies (GWAS). Data for 25(OH)D came from a GWAS comprising 417,580 participants, and data for epilepsy were obtained from the International League Against Epilepsy (ILAE) consortium. Five methods were used to analyze TSMR, including the inverse variance weighting method, MR Egger method, weighted median method, simple model, and weighted model. In the sensitivity analysis, MR Egger and MR PRESSO methods were used to test for pleiotropy, inverse variance weighting and MR Egger in Cochran's Q statistics were used to test for heterogeneity.

RESULTS: MR analyzed the relationship between 25(OH)D and different types of epilepsy, and the results showed that a 1 standard deviation increase in natural log-transformed serum 25(OH)D levels was associated with reduced risk for juvenile absence epilepsy (IVW OR = 0.985; 95% confidence interval (CI): 0.971-0.999; P-value = 0.038). There was no apparent heterogeneity and horizontal gene pleiotropy.

SIGNIFICANCE: Higher serum levels of 25(OH)D were a protective factor for adolescent absence epilepsy, but had no effect on other types of epilepsy.