The association between epilepsy and COVID-19: analysis based on Mendelian randomization and FUMA

Mingyao You; Ping Yuan; Liangqian Li; Baoduo Li; Zijun Peng; Hongbei Xu

doi:10.3389/fnins.2023.1235822

The association between epilepsy and COVID-19: analysis based on Mendelian randomization and FUMA

Front Neurosci. 2023 Sep 15:17:1235822. doi: 10.3389/fnins.2023.1235822. eCollection 2023.

Authors

Mingyao You^#¹, Ping Yuan^#¹, Liangqian Li^#¹, Baoduo Li¹, Zijun Peng¹, Hongbei Xu¹

Affiliation

¹ Department of Neurology, The Affiliated Hospital of Guizhou Medical University, Guizhou, China.

^# Contributed equally.

Abstract

Objective: A multitude of observational studies have underscored a substantial comorbidity between COVID-19 and epilepsy. This study was aimed at establishing a conclusive causal link between these two conditions.

Methods: We employed Mendelian randomization (MR) to evaluate the causal link between COVID-19 and epilepsy, as well as its focal and generalized subtypes. The GWAS for epilepsy and its subtypes database were abstracted from both FinnGen consortium and ILAE. Additionally, we leveraged functional mapping and annotation (FUMA) to integrate information from genome-wide association studies (GWAS) results.

Results: The MR analyses revealed that genetic liability to COVID-19 infection conferred a causal effect on epilepsy [FinnGen: OR: 1.5306; 95% confidence interval (CI): 1.1676-2.0062, P_FDR (false discovery rate) = 0.0076; ILAE: OR: 1.3440; 95% CI: 1.0235-1.7649, P_FDR = 0.0429], and generalized epilepsy (FinnGen: OR: 2.1155; 95% CI: 1.1734-3.8139, P_FDR = 0.0327; ILAE: OR: 1.1245; 95% CI: 1.0444-1.2108, P_FDR = 0.0114). Genetic liability to COVID-19 hospitalization conferred a causal effect on epilepsy (FinnGen: OR: 1.0934; 95% CI: 1.0097-1.1841, P_FDR = 0.0422; ILAE: OR: 1.7381; 95% CI: 1.0467-2.8862, P_FDR = 0.0451), focal epilepsy (ILAE: OR: 1.7549; 95% CI: 1.1063-2.7838, P_FDR = 0.0338), and generalized epilepsy (ILAE: OR: 1.1827; 95% CI: 1.0215-1.3693, P_FDR = 0.0406). Genetic liability to COVID-19 severity conferred a causal effect on epilepsy (FinnGen consortium: OR: 1.2454; 95% CI: 1.0850-1.4295, P_FDR = 0.0162; ILAE: OR: 1.2724; 95% CI: 1.0347-1.5647, P_FDR = 0.0403), focal epilepsy (FinnGen: OR: 1.6818; 95% CI: 1.1478-2.4642, P_FDR = 0.0231; ILAE: OR: 1.6598; 95% CI: 1.2572-2.1914, P_FDR = 0.0054), and generalized epilepsy (FinnGen: OR: 1.1486; 95% CI: 1.0274-1.2842, P_FDR = 0.0335; ILAE: OR: 1.0439; 95% CI: 1.0159-1.0728, P_FDR = 0.0086). In contrast, no causal linkage of epilepsy on COVID-19 was observed. Further, FUMA analysis identified six overlapping genes, including SMEK2, PNPT1, EFEMP1, CCDC85A, VRK2, and BCL11A, shared between COVID-19 and epilepsy. Tissue-specific expression analyses revealed that the disease-gene associations of COVID-19 were significantly enriched in lung, ovary, and spleen tissue compartments, while being significantly enriched in brain tissue for epilepsy.

Conclusion: Our study demonstrates that COVID-19 can be a contributing factor to epilepsy, but we found no evidence that epilepsy contributes to COVID-19.

Keywords: COVID-19; FUMA; Mendelian randomization; causal relationship; epilepsy.

Grants and funding

This study was supported by the National Natural Science Youth Fund Project (82001270); the National Natural Science Regional Foundation Project (82160242); the Basic Research Project of Guizhou Science and Technology Plan [Qiankehe Foundation ZK (2021) General 413]; and the Doctoral Research Start-up Fund (gyfybsky-2021-23).