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. 2024 Aug 23;14(1):19644.
doi: 10.1038/s41598-024-70370-1.

Causal relationship between immune cells and epilepsy mediated by metabolites analyzed through Mendelian randomization

Jiangwei Chen  1 , Haichun Yu  2 , Huihua Liu  3 , Han Yu  4 , Shuang Liang  5 , Qiong Wu  6 , Xian Zhang  7 , Rong Zeng  1 , Limei Diao  8   9
Affiliations

Causal relationship between immune cells and epilepsy mediated by metabolites analyzed through Mendelian randomization

Jiangwei Chen et al. Sci Rep. .

Abstract

Our study investigated the causal relationship between immune cells, metabolites, and epilepsy using two-sample Mendelian Randomization (MR) and mediation MR analysis of 731 immune cell traits and 1400 metabolites. Our core methodology centered on inverse-variance weighted MR, supplemented by other methods. This approach was crucial in clarifying the potential intermediary functions of metabolites in the genetic links between traits of immune cells and epilepsy. We found a causal relationship between immune cells and epilepsy. Specifically, the genetically predicted levels of CD64 on CD14-CD16- are positively correlated with the risk of epilepsy (p < 0.001, OR = 1.0826, 95% CI 1.0361-1.1312). Similarly, metabolites also exhibit a causal relationship with both immune cells (OR = 1.0438, 95% CI 1.0087-1.0801, p = 0.0140) and epilepsy (p = 0.0334, OR = 1.0897, 95% CI 1.0068-1.1795), and sensitivity analysis was conducted to further validate these relationships. Importantly, our intermediate MR results suggest that the metabolite Paraxanthine to linoleate (18:2n6) ratio may mediate the causal relationship between immune cell CD64 on CD14-CD16- and epilepsy, with a mediation effect of 5.05%. The results suggest the importance of specific immune cell levels and metabolites in understanding epilepsy's pathogenesis, which is significant for its prevention and treatment.

Keywords: Epilepsy; Immune cells; Mendelian randomization; Metabolites.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
(a) MR leave-one-out sensitivity analysis for immune cells (ebi-a-GCST90002001) on epilepsy. (b) MR leave-one-out sensitivity analysis for metabolites (GCST90200982) on epilepsy. (c) MR leave-one-out sensitivity analysis for ebi-a-GCST90002001 on GCST90200982.
Figure 2
Figure 2
(a) PPI Network: Displays the interactions between genes or proteins, helping to understand the key proteins and pathways in gene expression data. (b) Venn Diagram: Shows the overlap between metabolites and epilepsy-related genes. (c) GO Analysis: Depicts the enrichment of metabolites or genes in GO categories. (d) KEGG Pathway Enrichment Analysis: Illustrates the enrichment of metabolites or genes in KEGG pathways.
Figure 3
Figure 3
(a) Forest plot of different MR methods. (b) Depiction of the Mediating Role of the Metabolite (Paraxanthine to Linoleate (18:2n6) Ratio) in the Causal Relationship between Immune Cells (CD64 on CD14- CD16-) and Epilepsy, with MR Estimates of the Associations among Metabolites, Immune Cells, and Epilepsy provided by the Inverse-Variance Weighted Method.
Figure 4
Figure 4
Relationship Between Immune Cells, Metabolites, and Epilepsy. (Image by Figdraw).
See this image and copyright information in PMC

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References

    1. Fisher, R. S. et al. Epileptic seizures and epilepsy: Definitions proposed by the international league against epilepsy (ILAE) and the international bureau for epilepsy (IBE). Epilepsia46, 470–472 (2005). 10.1111/j.0013-9580.2005.66104.x - DOI - PubMed
    1. Scheffer, I. E. et al. ILAE classification of the epilepsies: Position paper of the ILAE commission for classification and terminology. Epilepsia58, 512–521 (2017). 10.1111/epi.13709 - DOI - PMC - PubMed
    1. Yin, F. et al. Auras in intractable frontal lobe epilepsy: Clinical characteristics, values, and limitations. Epilepsy Behav.115, 107724 (2021). 10.1016/j.yebeh.2020.107724 - DOI - PubMed
    1. Ahmedt-Aristizabal, D. et al. Motion Signatures for the Analysis of Seizure Evolution in Epilepsy. In 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) 2099–2105 (IEEE, Berlin, Germany, 2019). 10.1109/EMBC.2019.8857743. - PubMed
    1. Fiest, K. M. et al. Prevalence and incidence of epilepsy. Neurology88, 296–303 (2017). 10.1212/WNL.0000000000003509 - DOI - PMC - PubMed

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