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ORIGINAL RESEARCH article
Front. Genet.
Sec. Statistical Genetics and Methodology
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1399353
Thyroid function and hepatic fibrosis/cirrhosis: A twosample Mendelian randomization study
Provisionally accepted- Department of Nuclear Medicine, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
Background: Study evidences on the relationship of thyroid function with hepatic fibrosis/cirrhosis are still unclear and the conclusions are inconsistent. Herein, this Mendelian randomization (MR) research aimed to investigate the potential causal association between thyroid function and hepatic fibrosis/cirrhosis, in order to provide some new ideas for further exploration on improving strategies for prevention and control of this disease.Methods: Data from Genome-wide association study (GWAS) on exposures, including hyperthyroidism, hypothyroidism, and thyroid stimulating hormone (TSH) were extracted from the MRC Integrative Epidemiology Unit (MRC-IEU) (https://gwas.mrcieu.ac.uk/), and GWAS data for outcomes, including hepatic fibrosis/cirrhosis and chitinase-3-like protein 1 (CHI3L1) were obtained from the FinnGen consortium (https://www.finngen.fi/fi.). Inverse variance weighted (IVW), weighted median, and MR-Egger methods were utilized to examine the causal association of thyroid function with the risk of hepatic fibrosis/cirrhosis. Cochran's Q test was used to quantify the heterogeneity of instrumental variables (IVs), and that MR-PRESSO as well as leave-one-out for sensitivity analysis.Results: IVW estimates suggested that hypothyroidism had a potential causal association with higher odds of hepatic fibrosis/cirrhosis (OR=1.247, 95%CI: 1.087-1.431). The leave-one-out results indicated this potential causal relationship was relatively robust. In addition, we assessed the causal association between hypothyroidism and hepatic fibrosis/cirrhosis before and after eliminating outliers with heterogeneity, and found that after eliminating the outliers with heterogeneity, it was still significant (OR=1.266, 95%CI: 1.082-1.482, P=0.0046).Conclusions: Patients with hypothyroidism had potential higher risk of hepatic fibrosis/cirrhosis, and this finding may provide some references for disease's early screening as well as prevention. However, further studies exploring the specific mechanisms that hypothyroidism influencing hepatic fibrosis/cirrhosis are still needed.
Keywords: causal association, Hepatic fibrosis/cirrhosis, Hyperthyroidism, Hypothyroidism, Mendelian randomization study, Single nucleotide polymorphisms, Thyroid function
Received: 26 Mar 2024; Accepted: 11 Mar 2025.
Copyright: © 2025 Wang, Zhang, Li and Liu. 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:
Jun Liu, Department of Nuclear Medicine, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
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