Two-sample Mendelian Randomization Study: Iron Deficiency Anemia Increases the Risk of Epilepsy

Background: Several studies have suggested a possible association between iron deficiency anemia (IDA) and neurological dysfunction. In the present study, we aimed to investigate whether there is a causal relationship between IDA and epilepsy. We used a two-sample Mendelian randomization design. Methods: We obtained summary data of IDA and epilepsy from the FinnGen consortium. Genetic variants significantly associated with iron deficiency anemia were used as instrumental variables. Epilepsy, focal epilepsy, and generalized epilepsy were the outcomes. We used inverse variance weighting (IVW) as the primary estimate, and other MR methods were used as supplementary measures. Sensitivity analysis was also performed to assess heterogeneity and pleiotropy. Results: IVW estimates genetically predicted a causal relationship between iron deficiency anemia and the risk of epilepsy [odds ratio (OR), 1.153; 95% confidence interval (CI), 1.054–1.261; p = 0.002] and focal epilepsy (OR, 1.978, 95%CI, 1.576–2.482, p=3.975E-09), while no significant causal relationship was found with generalized epilepsy（OR, 1.103, 95%CI, 0.936-1.300, p=0.242）. There was no evidence of horizontal pleiotropy and heterogeneity in the sensitivity analysis. Conclusions: This two-sample Mendelian randomization study found that iron deficiency anemia has a negative effect on the development of epilepsy. Clinical control of iron deficiency anemia may be helpful in the prevention of epilepsy.