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. 2024 May 30:15:1388920.
doi: 10.3389/fneur.2024.1388920. eCollection 2024.

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

Xiangyi Wang #  1 , Wenting Xiong #  1 , Man Li  1 , Luyan Wu  1 , Yuying Zhang  1 , Chaofeng Zhu  1 , Wanhui Lin  1 , Shenggen Chen  1 , Huapin Huang  1   2   3
Affiliations

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

Xiangyi Wang et al. Front Neurol. .

Abstract

Background: Epilepsy is one of the most prevalent serious brain disorders globally, impacting over 70 million individuals. Observational studies have increasingly recognized the impact of plasma lipidome on epilepsy. However, establishing a direct causal link between plasma lipidome and epilepsy remains elusive due to inherent confounders and the complexities of reverse causality. This study aims to investigate the causal relationship between specific plasma lipidome and epilepsy, along with their intermediary mediators.

Methods: We conducted a two-sample Mendelian randomization (MR) and mediation MR analysis to evaluate the causal effects of 179 plasma lipidomes and epilepsy, with a focus on the inflammatory cytokine as a potential mediator based on the genome-wide association study. The primary methodological approach utilized inverse variance weighting, complemented by a range of other estimators. A set of sensitivity analyses, including Cochran's Q test, I 2 statistics, MR-Egger intercept test, MR-PRESSO global test and leave-one-out sensitivity analyses was performed to assess the robustness, heterogeneity and horizontal pleiotropy of results.

Results: Our findings revealed a positive correlation between Phosphatidylcholine (18:1_18:1) levels with epilepsy risk (OR = 1.105, 95% CI: 1.036-1.178, p = 0.002). Notably, our mediation MR results propose Tumor necrosis factor ligand superfamily member 12 levels (TNFSF12) as a mediator of the relationship between Phosphatidylcholine (18,1_18:1) levels and epilepsy risk, explaining a mediation proportion of 4.58% [mediation effect: (b = 0.00455, 95% CI: -0.00120-0.01030), Z = 1.552].

Conclusion: Our research confirms a genetic causal relationship between Phosphatidylcholine (18:1_18:1) levels and epilepsy, emphasizing the potential mediating role of TNFSF12 and provide valuable insights for future clinical investigations into epilepsy.

Keywords: MR analysis; Phosphatidylcholine (18:1_18:1); TNFSF12; causal relationship; epilepsy; mediation MR analysis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overall flow chart of this study. (A) Illustration of the study design and workflow. (B) Two-step Mendelian randomization assessment detailing the impact of Phosphatidylcholine (18:1_18:1) on hypertension through TNFSF12.
Figure 2
Figure 2
Causal effects of Phosphatidylcholine (18:1_18:1) on epilepsy. (A) Scatter plots; (B) forest plot; (C) leave-one-out analysis; (D) funnel plot.
Figure 3
Figure 3
Causal effects of TNFSF12 on epilepsy. (A) Scatter plots; (B) forest plot; (C) leave-one-out analysis; (D) funnel plot.
Figure 4
Figure 4
Forest plot for the causal effects of Phosphatidylcholine (18:1_18:1) on epilepsy mediated by TNFSF12.
See this image and copyright information in PMC

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References

    1. Thijs RD, Surges R, O'Brien TJ, Sander JW. Epilepsy in adults. Lancet. (2019) 393:689–701. doi: 10.1016/S0140-6736(18)32596-0 - DOI - PubMed
    1. Fisher RS, Boas WE, Blume W, Elger C, Genton P, Lee P, et al. . Epileptic seizures and epilepsy: definitions proposed by the international league against epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. (2005) 46:470–2. doi: 10.1111/j.0013-9580.2005.66104.x, PMID: - DOI - PubMed
    1. Asadi-Pooya AA, Brigo F, Lattanzi S, Blumcke I. Adult epilepsy. Lancet. (2023) 402:412–24. doi: 10.1016/S0140-6736(23)01048-6 - DOI - PubMed
    1. Murray CJ, et al. . Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the global burden of disease study 2010. Lancet. (2012) 380:2197–223. doi: 10.1016/S0140-6736(12)61689-4, PMID: - DOI - PubMed
    1. Manford M. Recent advances in epilepsy. J Neurol. (2017) 264:1811–24. doi: 10.1007/s00415-017-8394-2, PMID: - DOI - PMC - PubMed

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