Multi-omics insight into the metabolic and cellular characteristics in the pathogenesis of hypothyroidism.
Open accessAbstract
While circulating metabolites and immune system have been increasingly linked to hypothyroidism risk, the causality underlying these associations remains largely uninterrogated. We used Mendelian randomization to identified putative causal traits for hypothyroidism via integrating omics data. Briefly, we utilized 1180 plasma metabolites and 731 immune cells traits as exposures to identify putatively causal traits for hypothyroidism in the discovery (40,926 cases) and replication cohorts (14,871 cases). By combining MR results from two large-scale cohorts, we ultimately identified 21 putatively causal traits, including five plasma metabolites and 16 immune cell traits. CD3 on CD28+ CD4+ T cell and 1-(1-enyl-palmitoyl)-2-oleoyl-GPE (p-16:0/18:1) demonstrated the most pronounced positive and negative associations with hypothyroidism risk, respectively. The odds ratio and 95% confidence interval were 1.09 (1.07, 1.12) and 0.81 (0.75, 0.87), respectively. No evidence of horizontal pleiotropy, heterogeneity among instrumental variables or reverse causation were found for these 21 significant associations. Our study elucidates key metabolites and immune cell traits associated with hypothyroidism. These findings provide new insights into the etiology and potential therapeutic targets for hypothyroidism. This study elucidates key metabolites and immune cell traits associated with hypothyroidism. These findings provide new insights into the etiology and potential therapeutic targets for hypothyroidism.
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Autoimmune hypothyroidism may be present with rheumatoid arthritis (5%-26.2%).
“Autoimmunehypothyroidismmaybepresentwithother autoimmunediseases, such as type 1 diabetes (9.8%) and rheumatoidarthritis (5%-26.2%),reflectinganunderlyingimmunedysregulation and shared genetic factors. 12-15”
From Hypothyroidism: A Review (2025) · cites this paper as [12]
The Introduction (page unavailable) describes autoimmune thyroiditis as a common cause of hypothyroidism, but does not discuss rheumatoid arthritis. Searches for rheumatoid arthritis, co-occurrence, and the 5%–26.2% range found no passage addressing the claimed association or prevalence. (LLM, conf=0.74)
Experimental — accuracy not yet measuredAutoimmune hypothyroidism may be present with type 1 diabetes (9.8%).
“Autoimmunehypothyroidismmaybepresentwithother autoimmunediseases, such as type 1 diabetes (9.8%) and rheumatoidarthritis (5%-26.2%),reflectinganunderlyingimmunedysregulation and shared genetic factors. 12-15”
From Hypothyroidism: A Review (2025) · cites this paper as [12]
The Introduction (page unavailable) links hypothyroidism to autoimmune thyroiditis, but does not discuss co-occurrence with type 1 diabetes. Searches for type 1 diabetes, 9.8%, and the claimed autoimmune-disease association returned no supporting passage; the Results discuss other diabetes-related conditions instead. (LLM, conf=0.72)
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- Authors
- Zheng, S., Liu, L., Liang, K., Yan, J., Meng, D., Liu, Z., Tian, S., & Shan, Y.
- Affiliations
- Wenzhou Medical University (CN)
- Corresponding author
- Tian, Sicong
- Shan, Yujuan
- Venue
- Communications Biology
- Published
- 2024-08-14
- Volume
- 7
- Issue
- 1
- Pages
- 990-990
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC11324791
- OpenAlex
- W4401577169
- Cited by
- 15
- References
- 52
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 1
- FWCI
- 4.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Communications Biology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82304149)
- Natural Science Foundation of Zhejiang Province (LQ23H260003)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- hypothyroidism, pathogenesis, plasma metabolites, immune cell traits, CD4+ T cells, phosphatidylglycerol, lipid metabolism, Mendelian randomization, multi-omics integration, etiology
- MeSH terms
- Multiomics, Female, Humans, Hypothyroidism, Male, Metabolomics, Mendelian Randomization Analysis
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