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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1375915
This article is part of the Research Topic Community Series in Towards Precision Medicine for Immune-Mediated Disorders: Advances in Using Big Data and Artificial Intelligence to Understand Heterogeneity in Inflammatory Responses, Volume II View all 12 articles
Global and regional genetic association analysis of ulcerative colitis and type 2 diabetes mellitus and causal validation analysis of two-sample two-way Mendelian randomization
Provisionally accepted
Yanzhi Hu
1
Zhe Chen
2
Minghan Zhou
1*
Zhenyu Zhao
3
Xiaoyan Wang
1*
Jun Huang
1*
Xintian Li
1*
Juanni Zeng
1,4*- 1 The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China, Changsha, China
- 2 Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
- 3 College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- 4 Laboratory of Vascular Biology and Translational Medicine, Medical School, Hunan University of Chinese Medicine, Changsha, China
Background: This study investigates the causal link between Ulcerative Colitis (UC) and Type 2 Diabetes Mellitus (T2DM) using LDSC, LAVA, and TSMR analyses, aiming to inform clinical strategies. Methods: Genetic data from GWAS for T2DM and UC in European populations were analyzed. The UC dataset included 27,432 samples and 8,050,003 SNPs, while T2DM had 406,831 samples and 11,914,699 SNPs. LDSC and LAVA assessed genetic correlations. MR analysis with IVW, MR-Egger, Weighted median, and Weighted mode estimated causal effects. Heterogeneity and pleiotropy were examined using various tests. Results: LDSC revealed no significant genetic association between UC and T2DM (rg = -0.0518, P = 0.3569). LAVA identified 9 regions with local genetic correlations, suggesting a negative correlation. MR analysis indicated a negative causal relationship from T2DM to UC (IVW OR = 0.917, P < 0.05). No pleiotropy or heterogeneity was detected. Reverse MR analysis with UC as exposure and T2DM as outcome showed no clear causal link. Conclusion: T2DM may decrease UC risk, with no significant causal effect from UC to T2DM.
Keywords: uc, T2DM, Mendelian randomization, LDSC analysis, LAVA analysis
Received: 24 Jan 2024; Accepted: 04 Nov 2024.
Copyright: © 2024 Hu, Chen, Zhou, Zhao, Wang, Huang, Li and Zeng. 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:
Minghan Zhou, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China, Changsha, China
Xiaoyan Wang, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China, Changsha, China
Jun Huang, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China, Changsha, China
Xintian Li, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China, Changsha, China
Juanni Zeng, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China, Changsha, China
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