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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Clinical Diabetes
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1396912
This article is part of the Research Topic Biomarkers, Mechanisms, and Treatment Strategies for Epilepsy - Volume II View all 5 articles

Identifying the genetic association between severe autoimmune type 2 diabetes and the risk of focal epilepsy

Provisionally accepted
Huanhua Wu Huanhua Wu 1,2Kai Liao Kai Liao 2Ying Li Ying Li 3*Zhi q. Tan Zhi q. Tan 2Ziqing Zhou Ziqing Zhou 3Chunyuan zeng Chunyuan zeng 2*Jian Gong Jian Gong 2Huadong Wang Huadong Wang 4*Hao Xu Hao Xu 2*Youzhu Hu Youzhu Hu 1,5*
  • 1 The Affiliated Shunde Hospital of Jinan University, Foshan, Guangdong Province, China
  • 2 Department of Nuclear Medicine, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China
  • 3 Jinan University, Guangzhou, Guangdong Province, China
  • 4 Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, Guangdong Province, China
  • 5 First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China

The final, formatted version of the article will be published soon.

    Observational studies suggested a bidirectional relationship between severe autoimmune type 2 diabetes and focal epilepsy. However, it remains debated whether and in which direction a causal association exists. This genetics-based study aimed to explore the relationships of severe autoimmune type 2 diabetes (T2DM) and focal epilepsy outcomes with two sample Mendelian randomisation (TSMR) method.Genetic instruments were obtained from large-scale genome-wide meta-analysis of severe autoimmune T2DM (Ncase = 452, Ncontrol = 2,744), and focal epilepsy (Ncase = 929, Ncontrol = 212,532) of European ancestry. A series of analyses were performed to select eligible genetic instruments robustly associated with each of the traits using summary-level statistics. Inverse variance weighted was used for primary analysis, with alternative 11 MR methods. A scatter plot was utilized to illustrate the association between single nucleotide polymorphism (SNP) effects on the exposure and SNP effects on the outcome. The Wald ratio for individual SNPs and their cumulative effects was depicted using a forest plot. And diagnostics and sensetivity analyses were used to evaluate if the causal estimates are robust to violations of MR underlying assumptions, including pleiotropy, heterogeneity assessment, and leave-one-out analysis. Then the results were validated using CURATED database of DisGeNET platform.For forward analysis, genetic predisposition to severe autoimmune T2DM was associated with an increased risk of focal epilepsy (Inverse variance weighted (IVW) method: OR = 1.11, 95% CI = 1.03-1.18, p = 0.012). For reverse analysis, there was no enough instrument variables of focal epilepsy on severe autoimmune T2DM. Further, the interrelation between severe autoimmune T2DM and focal epilepsy was demonstrated via variant-disease association network analysis using the instrument SNPs.This MR study supports a causal link between severe autoimmune T2DM and focal epilepsy. More effort should be made to screen seizure in severe autoimmune T2DM, unravel its clinical implications, and explore its role as a putative modifiable risk factor.

    Keywords: Severe autoimmune type 2 diabetes, focal epilepsy, Two Sample Mendelian Randomization, causal associations, GWAS

    Received: 06 Mar 2024; Accepted: 14 Oct 2024.

    Copyright: © 2024 Wu, Liao, Li, Tan, Zhou, zeng, Gong, Wang, Xu and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Ying Li, Jinan University, Guangzhou, 510632, Guangdong Province, China
    Chunyuan zeng, Department of Nuclear Medicine, First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong Province, China
    Huadong Wang, Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong Province, China
    Hao Xu, Department of Nuclear Medicine, First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong Province, China
    Youzhu Hu, The Affiliated Shunde Hospital of Jinan University, Foshan, Guangdong Province, China

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