Exploring the causal effects of epilepsy and its subtypes on anthropometric traits: A 2-sample Mendelian randomization study

Epilepsy is frequently associated with altered anthropometric outcomes, including height, weight, and body mass index (BMI). However, the causal relationship between epilepsy and these traits remains uncertain. This Mendelian randomization (MR) study aimed to investigate the causal effects of epilepsy and its subtypes on anthropometric traits, including height, weight, BMI, idiopathic short stature, constitutional tall stature, and obesity. A 2-sample MR analysis was conducted using genetic instruments derived from genome-wide association studies. Genetic instruments for epilepsy phenotypes were sourced from the European-only summary statistics of the International League Against Epilepsy Consortium on Complex Epilepsies. Outcome data were obtained from the FinnGen database and replicated in the pan-UK Biobank. The inverse-variance weighted method was used as the primary analysis, while MR-Egger regression, weighted median, and MR-PRESSO were employed to assess robustness and horizontal pleiotropy. MR analyses did not identify significant causal associations between epilepsy (including subtypes) and any anthropometric outcomes after adjusting for multiple testing. Although nominally significant associations appeared in specific analyses (e.g., focal epilepsy with weight and generalized genetic epilepsy with BMI), none survived correction. Sensitivity analyses confirmed the absence of directional pleiotropy or influential outliers. This MR study provides no evidence supporting a direct causal effect of epilepsy or its subtypes on anthropometric traits. These results indicate that observed correlations from previous studies may reflect confounding factors, such as antiepileptic medications or lifestyle, rather than epilepsy itself. Future research should investigate alternative mechanisms underlying growth and weight changes in individuals with epilepsy.