Causal effect of psychiatric disorders on epilepsy: A two‐sample Mendelian randomization study

Abstract

Background This study aims to explore the relationship between psychiatric disorders and the risk of epilepsy using Mendelian randomization (MR) analysis. Methods We collected summary statistics of seven psychiatric traits from recent largest genome‐wide association study (GWAS), including major depressive disorder (MDD), anxiety disorder, autism spectrum disorder (ASD), bipolar disorder (BIP), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and insomnia. Then, MR analysis estimates were performed based on International League Against Epilepsy (ILAE) consortium data ( n case = 15,212 and n control = 29,677), the results of which were subsequently validated in FinnGen consortium ( n case = 6260 and n control = 176,107). Finally, a meta‐analysis was conducted based on the ILAE and FinnGen data. Results We found significant causal effects of MDD and ADHD on epilepsy in the meta‐analysis of the ILAE and FinnGen, with corresponding odds ratios (OR) of 1.20 (95% CI 1.08–1.34, p = .001) and 1.08 (95% CI 1.01–1.16, p = .020) by the inverse‐variance weighted (IVW) method respectively. MDD increases the risk of focal epilepsy while ADHD has a risk effect on generalized epilepsy. No reliable evidence regarding causal effects of other psychiatric traits on epilepsy was identified. Conclusions This study suggests that major depressive disorder and attention deficit hyperactivity disorder may causally increase the risk of epilepsy.

Role of inflammatory cytokine in mediating the effect of plasma lipidome on epilepsy: a mediation Mendelian randomization study

“…Furthermore, we conducted a leave-one-out analysis to identify SNPs with potential extreme influence on estimates and to evaluate the robustness of the results. Finally, scatter plots were used to demonstrate that the results were not affected by outliers and funnel 1 https://storage.googleapis.com/finngen-public-data-r10/summary_stats/ finngen_R10_G6_EPLEPSY.gz plots were used to illustrate the robustness of the correlation and absence of heterogeneity (22). All statistical analyses were performed using the MR and MR-PRESSO packages.…”

“…All analyses were conducted using R 4.3.3 software. To assess the causal relationship between plasma lipidomes and epilepsy, inverse variance weighting (IVW) was primarily conducted using the ‘TwoSampleMR’ package (version 0.5.8) ( 20 , 22 , 28 ). Additionally, four other MR methods-MR-Egger, weighted median, simple mode and weighted mode-were employed to complement the final findings.…”

“…In the MR study, single nucleotide polymorphisms (SNPs) are regarded as an instrumental variables (IVs) to estimate the causal relationship between exposure and outcome (19). Previous studies have found the causal relationship between human blood metabolites, gut microbiota, circulating lipids, psychiatric disorders and epilepsy (20)(21)(22)(23)(24). In recent years, an increasing number of studies have examined the association between plasma lipidome and epilepsy, yet no research has explored this relationship at the genetic level.…”

Impact of Physical Activity Frequency, Duration, and Intensity on Senile Cataract Risk: A Mendelian Randomization Study

“…In a separate GWAS involving 377,234 individuals of European descent, researchers used Axivity AX3 wrist-worn triaxial accelerometers to calculate the PA level and defined a measure called the overall acceleration average (OAA). 23 , 24 …”