Two-sample Mendelian randomization study: iron deficiency anemia increases the risk of epilepsy

PurposeIron deficiency anemia (IDA) is the most common form of anemia in the world, affecting children, women and the elderly, while also being a common comorbidity in several medical conditions. Several studies have suggested a possible association between IDA and neurological dysfunction. Epilepsy, one of the common neurological disorders, has an unknown association with IDA. This pa per aims to investigate whether there is a causal relationship between IDA and epilepsy using a two-sample Mendelian randomization (MR) design.Design/methodology/approachThis paper obtained summary data on IDA and epilepsy from the FinnGen consortium. Genetic variants significantly associated with IDA were used as instrumental variables (IVs). Epilepsy, focal epilepsy and generalized epilepsy were the outcomes. This paper used inverse variance weighted (IVW) as the primary estimate, and other MR methods were used as supplementary measures. Sensitivity analysis was also performed to assess heterogeneity and pleiotropy.FindingsIVW estimates genetically predicted a causal relationship between IDA and the risk of epilepsy [odds ratio (OR), 1.15; 95% confidence interval (95% CI), 1.05-1.26; p = 0.002] and focal epilepsy (OR, 1.978, 95% CI, 1.58-2.48, p <= 0.0001), while no significant causal relationship was found with generalized epilepsy (OR, 1.1, 95% CI, 0.94-1.3, p = 0.24). There was no evidence of horizontal pleiotropy and heterogeneity in the sensitivity analysis.Originality/valueThis two-sample MR study found that IDA has a negative effect on the development of epilepsy. Clinical control of IDA may be helpful in the prevention of epilepsy. There is a need for further studies to explain the underlying mechanisms of this association.