ABO and RhD Blood Groups in Epilepsy: A Comprehensive Case–Control Analysis

Background: Although ABO blood groups have been implicated in several vascular and neurological disorders, evidence regarding their association with epilepsy remains limited and inconclusive. We performed the largest and most comprehensive case–control evaluation to date to determine whether ABO/RhD blood groups are associated with epilepsy. Methods: We conducted a retrospective hospital-based case–control study including 806 adults with epilepsy and 14,032 controls from the same institutional population between January 2015 and January 2026. Epilepsy diagnoses were confirmed independently by two neurologists according to International League Against Epilepsy criteria. Associations between epilepsy and ABO/RhD blood groups were evaluated using a comprehensive analytical framework incorporating multivariable-adjusted logistic regression, binary blood group comparisons, age- and sex-matched sensitivity analyses, and epilepsy subtype-specific analyses. Results: No significant association was identified between epilepsy and ABO/RhD blood groups across any analytical approach. Overall ABO blood group (p = 0.777) and RhD status (p = 0.611) distributions were comparable between patients with epilepsy and controls. Binary analyses showed no significant associations for non-O versus O (OR 1.05, 95% CI 0.90–1.22; p = 0.535), non-A versus A (OR 0.93, 95% CI 0.80–1.06; p = 0.297), non-B versus B (OR 1.03, 95% CI 0.85–1.25; p = 0.748), non-AB versus AB (OR 1.05, 95% CI 0.81–1.34; p = 0.723), or RhD-negative versus RhD-positive status (OR 1.06, 95% CI 0.85–1.31; p = 0.611). These findings remained unchanged after multivariable-adjusted logistic regression, 1:4 age- and sex-matched sensitivity analyses (806 patients with epilepsy and 3224 matched controls; ABO p = 0.774, RhD p = 0.740), and comparisons between focal and generalized epilepsy subtypes (ABO p = 0.531; RhD p = 0.995). Conclusions: In this large hospital-based case–control study, no significant association was identified between epilepsy and ABO/RhD blood groups. However, the hospital-based control population and the availability of blood group data should be considered when interpreting these findings.