Causal relationship between addictive behaviors and epilepsy risk: A mendelian randomization study

Epilepsy Behav. 2023 Oct:147:109443. doi: 10.1016/j.yebeh.2023.109443. Epub 2023 Sep 18.


Background: Previous studies have reported inconsistent results regarding the potential relationships between addictive behaviors and the risk of epilepsy.

Objective: To assess whether genetically predicted addictive behaviors are causally associated with the risk of epilepsy outcomes.

Methods: The causation between five addictive behaviors (including cigarettes per day, alcoholic drinks per week, tea intake, coffee intake, and lifetime cannabis use) and epilepsy was evaluated by using a two-sample Mendelian Randomization (MR) analysis. The inverse-variance weighted (IVW) method was used as the primary outcome. The other MR analysis methods (MR Egger, weighted median, simulation extrapolation corrected MR-Egger, and Mendelian Randomization Pleiotropy Residual Sum and Outlier (MR-PRESSO)) were performed to complement IVW. In addition, the robustness of the MR analysis results was assessed by leave-one-out analysis.

Results: The IVW analysis method indicated an approximately 20% increased risk of epilepsy per standard deviation increase in lifetime cannabis use (odds ratio [OR], 1.20; 95% confidence interval [CI]), 1.02-1.42, P = 0.028). However, there is no causal association between the other four addictive behaviors and the risk of epilepsy (cigarettes per day: OR, 1.04; 95% CI, 0.92-1.18, P = 0.53; alcoholic drinks per week: OR, 1.31; 95% CI, 0.93-1.84, P = 0.13; tea intake: OR, 1.15; 95% CI, 0.84-1.56, P = 0.39; coffee intake: OR, 0.86; 95% CI, 0.59-1.23, P = 0.41). The other MR analysis methods and further leave-one-out sensitivity analysis suggested the results were robust.

Conclusion: This MR study indicated a potential genetically predicted causal association between lifetime cannabis use and higher risk of epilepsy. As for the other four addictive behaviors, no evidence of a causal relationship with the risk of epilepsy was found in this study.

Keywords: Addictive behaviors; Cannabis; Causal; Epilepsy; Mendelian randomization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Behavior, Addictive* / genetics
  • Cannabinoid Receptor Agonists
  • Cannabis*
  • Coffee / adverse effects
  • Epilepsy* / epidemiology
  • Epilepsy* / genetics
  • Genome-Wide Association Study
  • Humans
  • Mendelian Randomization Analysis
  • Tea


  • Coffee
  • Cannabinoid Receptor Agonists
  • Tea