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ORIGINAL RESEARCH article

Front. Med.
Sec. Nephrology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1429369
This article is part of the Research Topic Highlights in Diabetes Nephropathy View all 5 articles

The Association Between Type 1 Diabetes Mellitus and the Risk of IgA Nephropathy: A Mendelian Randomization Study

Provisionally accepted
Chun-Hua Zhang Chun-Hua Zhang *Yang Shen Yang Shen Su-Mei Zhao Su-Mei Zhao
  • Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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

    Objective: To investigate the potential causal relationship between Type 1 Diabetes Mellitus (T1DM) and IgA Nephropathy (IgAN) to deepen understanding of the association between these two conditions and to provide a scientific basis for future preventive and therapeutic strategies. Methods: This study employed Mendelian Randomization (MR) analysis, using single nucleotide polymorphisms (SNPs) derived from genome-wide association studies (GWAS) as genetic instrumental variables (IVs), to assess the association between T1DM and IgAN. The analytical approaches included univariable and multivariable MR, along with sensitivity analyses such as Mendelian Randomization-Egger (MR-Egger) and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), to evaluate the impact of heterogeneity and pleiotropy. Results: Univariable MR analysis using the IVW method revealed an odds ratio (OR) of 1.39 (95% confidence interval (CI): 1.10–1.74) for the association between T1DM and IgAN. Adjusted results from multivariable MR analysis indicated a significant relationship between T1DM and increased risk of IgAN; for example, after adjusting for triglycerides (TG), the OR was 1.534 (CI: 1.213–1.543). After adjustment for HOMA-IR, the OR was 1.303 (CI: 1.149–1.198). Sensitivity analyses, including MR-Egger regression intercept testing (P=0.476), suggested no pleiotropy, and MR-PRESSO did not detect any influence from outlier SNPs. Conclusion: The findings suggest that T1DM is a factor in increasing the risk of IgAN, enhancing our understanding of the potential relationship between T1DM and IgAN and providing possible biological pathways for future disease prevention and intervention.

    Keywords: type 1 diabetes mellitus, IgA nephropathy, Mendelian randomization, Single nucleotide polymorphisms, genome-wide association studies

    Received: 08 May 2024; Accepted: 01 Oct 2024.

    Copyright: © 2024 Zhang, Shen and Zhao. 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: Chun-Hua Zhang, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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