The genetic link between systemic autoimmune disorders and temporal lobe epilepsy: A bioinformatics study

Malekpour, Mahdi; Salarikia, Seyed Reza; Kashkooli, Mohammad; Asadi‐Pooya, Ali A.

doi:10.1002/epi4.12727

Cited by 4 publications

(1 citation statement)

References 65 publications

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“…Malekpour et al. ( 16 ) explored the relationship between frontal lobe epilepsy and three immune disorders, including RA, and showed that there were common genetic variants among the conditions. In addition, a meta-analysis emphasized that patients with RA have a higher risk of epilepsy than non-RA patients, and there was a negative correlation with age.…”

Section: Discussionmentioning

confidence: 99%

Causal relationship between rheumatoid arthritis and epilepsy in a European population: a univariate and multivariate Mendelian randomization study

Liu,

Ye,

et al. 2024

Front. Immunol.

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BackgroundSeveral previous studies have reported an association between rheumatoid arthritis (RA) and epilepsy, but the causal relationship is unclear. The aim of this study was to assess the connection between RA and epilepsy in a European population using Mendelian randomization (MR).MethodsGenome-wide association study summary data on RA and epilepsy from European populations were included. Univariate MR (UVMR) and multivariate MR were used to investigate the causal relationship between the two conditions. Three analysis methods were applied: inverse variance weight (IVW), MR-Egger, and weighted median, with IVW being the primary method. Cochran Q statistics, MR-PRESSO, MR-Egger intercept, leave-one-out test, and MR-Steiger test were combined for the sensitivity analysis.ResultsUVMR showed a positive association between RA and epilepsy risk (OR=1.038, 95% CI=1.007–1.038, p=0.017) that was supported by sensitivity analysis. Further MVMR after harmonizing the three covariates of hypertension, alcohol consumption, and smoking, confirmed the causal relationship between RA and epilepsy (OR=1.049, 95% CI=1.011–1.087, p=0.010).ConclusionThis study demonstrated that RA is associated with an increased risk of epilepsy. It has emphasized that the monitoring of epilepsy risk in patients diagnosed with RA should be strengthened in clinical practice, and further studies are needed in the future to explore the potential mechanism of action connecting the two conditions.

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Section: Discussionmentioning

confidence: 99%

Causal relationship between rheumatoid arthritis and epilepsy in a European population: a univariate and multivariate Mendelian randomization study

Liu,

Ye,

et al. 2024

Front. Immunol.

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The genetic link between systemic autoimmune disorders and temporal lobe epilepsy: A bioinformatics study

et al. 2023

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Objective:We aimed to explore the underlying pathomechanisms of the comorbidity between three common systemic autoimmune disorders (SADs) [i.e., insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA)] and temporal lobe epilepsy (TLE), using bioinformatics tools. We hypothesized that there are shared genetic variations among these four conditions. Methods: Different databases (DisGeNET, Harmonizome, and Enrichr) were searched to find TLE-associated genes with variants; their single nucleotide polymorphisms (SNPs) were gathered from the literature. We also did a separate literature search using PubMed with the following keywords for original articles: "TLE" or "Temporal lobe epilepsy" AND "genetic variation," "single nucleotide polymorphism," "SNP," or "genetic polymorphism." In the next step, the SNPs associated with TLE were searched in the LitVar database to find the shared gene variations with RA, SLE, and IDDM.Results: Ninety unique SNPs were identified to be associated with TLE. LitVar search identified two SNPs that were shared between TLE and all three SADs (i.e., IDDM, SLE, and RA). The first SNP was rs16944 on the Interleukin-1β (IL-1β) gene. The second genetic variation was ε4 variation of apolipoprotein E (APOE) gene.Significance: The shared genetic variations (i.e., rs16944 on the IL-1β gene and ε4 variation of the APOE gene) may explain the underlying pathomechanisms of the comorbidity between three common SADs (i.e., IDDM, SLE, and RA) and TLE. Exploring such shared genetic variations may help find targeted therapies for patients with TLE, especially those with drug-resistant seizures who also have comorbid SADs.

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Systemic lupus erythematosus and epilepsy: A Mendelian randomization study

Hu,

Lin,

et al. 2024

Epilepsia Open

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ObjectiveNumerous observational studies have found a relationship between systemic lupus erythematosus (SLE) and epilepsy; however, their causal relationship remains unclear. This study aimed to investigate the causal role of SLE in epilepsy or any of its subtypes using a two‐sample Mendelian randomization (MR) analysis.MethodsSingle nucleotide polymorphisms (SNPs) linked to SLE were utilized as instrumental variables in MR analysis to assess their causal impact on epilepsy. The primary MR findings were derived using the inverse variance weighted (IVW) method, which was further supported by the weighted median and MR‐Egger regression techniques. Additionally, sensitivity analyses, including Cochran's Q test and pleiotropy tests, were conducted to evaluate the influence of these SNPs on epilepsy, particularly looking for signs of horizontal pleiotropy and heterogeneity.ResultsWe selected 43 SNPs that reached genome‐wide significance from genome‐wide association studies (GWASs) on SLE to serve as instrumental variables in this study. The IVW method showed no evidence to support a causal association between SLE and epilepsy (all epilepsy: odds ratio (OR) = 1.006, 95% confidence interval (CI) = 0.994–1.018; focal epilepsy: OR = 1.006, 95% CI = 0.994–1.019; generalized epilepsy: OR = 1.015, 95% CI = 0.996–1.035). Other MR complementary methods revealed consistent results. Furthermore, there was no evidence indicating heterogeneity or horizontal pleiotropy.SignificanceThe findings of MR analysis did not support a genetically predicted causal relationship between SLE and epilepsy, but emphasized the need for further research on shared pathophysiological mechanisms, particularly the role of immune system abnormalities and potential influences such as chronic inflammation and therapeutic interventions.Plain Language SummaryThe etiology of epilepsy is complex and diverse, including immune factors. Through a Mendelian randomization analysis, we did not find evidence of a genetic causal relationship between systemic lupus erythematosus and epilepsy. However, this does not invalidate epidemiological evidence, and further exploration is needed to investigate factors influencing the relationship between the two.

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The genetic link between systemic autoimmune disorders and temporal lobe epilepsy: A bioinformatics study

Cited by 4 publications

References 65 publications

Causal relationship between rheumatoid arthritis and epilepsy in a European population: a univariate and multivariate Mendelian randomization study

Causal relationship between rheumatoid arthritis and epilepsy in a European population: a univariate and multivariate Mendelian randomization study

The genetic link between systemic autoimmune disorders and temporal lobe epilepsy: A bioinformatics study

Systemic lupus erythematosus and epilepsy: A Mendelian randomization study

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