Journal of Shanghai Jiao Tong University (Medical Science) >

2025 , Vol. 45 >Issue 6: 766 - 773

DOI: https://doi.org/10.3969/j.issn.1674-8115.2025.06.012

Evidence-based medicine

Mendelian randomization analysis of causal relationship between celiac disease and autoimmune thyroid disease

  • YAN Junhao ,
  • GUO Xiaolei ,
  • LUO Zhaofeng ,
  • TANG Jian ,
  • WANG Zheng
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  • 1.Department of Gastroenterology and Thyroid Surgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
    2.Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
First author contact:YAN Junhao, GUO Xiaolei and LUO Zhaofeng were responsible for data collection and statistical analysis, as well as manuscript revision. YAN Junhao conducted literature search and manuscript writing. YAN Junhao, TANG Jian and WANG Zheng were responsible for the research design and final review of the paper. All authors have read and approved the final version of the manuscript to submission.
YAN Junhao, E-mail: yanjh5212014@126.com.

Received date: 2024-11-03

  Accepted date: 2025-03-17

  Online published: 2025-06-28

Supported by

National Natural Science Foundation of China(82270552)

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Abstract

Objective ·To investigate the bidirectional causal relationships between celiac disease (CeD) and Hashimoto thyroiditis (HT) as well as Graves disease (GD), using a two-sample Mendelian randomization (MR) approach. Methods ·Single nucleotide polymorphisms (SNPs) related to CeD, HT and GD were extracted from publicly available Genome-Wide Association Studies (GWAS) databases and used as instrumental variables. The inverse-variance weighted (IVW) method served as the primary analytical approach, supplemented by MR-Egger, weighted median (WME) and weighted mode (WMO) methods, to evaluate the causal associations between CeD and both HT and GD. Replication analyses using alternative GWAS datasets were conducted to validate the robustness of the results. Heterogeneity was assessed using Cochran's Q test, and pleiotropy was evaluated via MR-Egger intercept test. Leave-one-out analyses were performed to assess the impact of individual SNPs on the results. Results ·The IVW analysis results indicated that genetically predicted CeD significantly increased the risk of HT [discovery group: OR=1.186 (95%CI 1.114‒1.262), P<0.001; replication group: OR=1.218 (95%CI 1.090‒1.361), P<0.001] and GD [discovery group: OR=1.214 (95%CI 1.155‒1.276), P<0.001; replication group: OR=1.273 (95%CI 1.161‒1.396), P<0.001]. However, reverse MR analyses did not provide evidence for a causal relationship between HT and CeD, while genetically predicted GD significantly increased the risk of CeD [discovery group: OR=1.259 (95%CI 1.006‒1.576), P=0.044; replication group: OR=1.387 (95%CI 1.233‒1.560), P<0.001]. Sensitivity analyses suggested that the results were not influenced by horizontal pleiotropy. Conclusion ·CeD may be causally associated with a higher risk of HT and GD, while GD may increase the risk of developing CeD. HT does not appear to have an impact on CeD.

Key words： celiac disease (CeD); Hashimoto thyroiditis (HT); Graves disease (GD); Mendelian randomization (MR)

Cite this article

YAN Junhao , GUO Xiaolei , LUO Zhaofeng , TANG Jian , WANG Zheng . Mendelian randomization analysis of causal relationship between celiac disease and autoimmune thyroid disease[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025 , 45(6) : 766 -773 . DOI: 10.3969/j.issn.1674-8115.2025.06.012

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