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ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Thyroid Endocrinology
Volume 15 - 2024 |
doi: 10.3389/fendo.2024.1361581
Hypothyroidism and dermato/polymyositis: A two-sample Mendelian randomization study
Provisionally accepted- 1 Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- 2 Zhongshan Hospital, Fudan University, Shanghai, Shanghai Municipality, China
- 3 Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Dongyuan, China
Objective: Observational studies have revealed a higher probbility of hypothyroidism in patients with dermatomyositis (DM) or polymyositis (PM), but there is no consensus on whether hypothyroidism causally influences DM or PM. In the present study, we assessed the causal association between hypothyroidism and the risk of dermatomyositis or polymyositis using twosample Mendelian randomization (TSMR).The genome-wide association data of hypothyroidism and dermatomyositis/polymyositis were obtained from the IEU Open GWAS project. Then, TSMR was used to determine whether hypothyroidism is causally associated with DM or PM. Singlenucleotide polymorphisms (SNPs) significantly associated with hypothyroidism were identified and used as instrumental variables (IVs), and the causal relationship between hypothyroidism and DM/PM was examined using TSMR. MR pleiotropy and Cochran's Q test were used to confirm the heterogeneity and pleiotropy of identified IVs, then four different models, including the inverse variance weighted model (IVW), MR-Egger, weighted median and weighted model were applied in this MR analysis. Results: Sixty-eight SNPs for DM and 68 SNPs for PM were selected as the IVs (P<5×10 -8 ; linkage disequilibrium R 2 <0.001) to assess the causal association between hypothyroidism and DM/PM selected from GWASs on hypothyroidism. The results revealed a positive causal effect of hypothyroidism on both DM and PM (DM: OR 2.563, 95% CI [1.348, 4.874], P = 0.00156; PM: OR1.709, 95% CI [1.157, 2.525], P =0.007). Moreover, there was no heterogeneity or pleiotropy in the results.In conclusion, the MR analysis results provided strong evidence to indicate that hypothyroidism might be causally associated with DM and PM. These findings may have important implications for the pathogenesis and possible future therapies of DM/PM.
Keywords: Dermatomyositis, Polymyositis, Hypothyroidism, Mendelian randomization, Immune Disease
Received: 25 Jan 2024; Accepted: 21 Aug 2024.
Copyright: © 2024 Li, Yang, Ma, Huang, Zhi, Wang and Lu. 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:
Yan Ma, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200000, China
Suli Wang, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200000, China
Liangjing Lu, Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Dongyuan, China
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