Risk of epilepsy in rheumatoid arthritis: a meta-analysis of population based studies and bioinformatics analysis

BACKGROUND: An increasing number of studies support an association between rheumatoid arthritis (RA) and brain disorders. This study aims to determine the association between RA and epilepsy. METHODS: A comprehensive search of databases in both English and Chinese was performed. Data from the selected studies were extracted and analyzed independently by two authors. Genes associated with epilepsy and RA were also collected and analyzed. RESULTS: We included six nationwide population based studies (n = 7,094,113 cases in total) for the meta-analysis. The risk of epilepsy was increased in RA patients [risk ratio (RR) = 1.601; 95% confidence interval (CI): 1.089–2.354; p = 0.017; n = 3,803,535 cases] and children born to mothers with RA (RR = 1.475; 95% CI: 1.333–1.633; p < 0.001, n = 3,290,578 cases). Subgroup analysis and meta-regression showed the RR of epilepsy in RA was negatively correlated with age. Furthermore, we found that 433 identified genes in a coexpression network from the hippocampi of 129 epileptic patients were enriched in the RA and related Kyoto Encyclopedia of Genes and Genomes pathways, while 13 genes (mainly related to inflammatory cytokines and chemokines) were identified as potential key genes bridging the RA and epilepsy. CONCLUSIONS: Our study, utilizing meta-analysis and bioinformatical data, highlights a close association between epilepsy and RA. Further studies are still warranted to expand these findings, especially for a population that is exposed to RA during fetal and childhood periods.