Evidence map›Paper›PMID 39478467›Full record

ArticleBMC gastroenterology2024

Causal relationship between hypothyroidism and ulcerative colitis: a bidirectional Mendelian randomization study.

Yumeng Yang, Jianhui Li, Xin Wang, Jing Ma

Abstract read
In one paragraph

Article in BMC gastroenterology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Yumeng YangXi'an Medical University, Xi'an, 710021, Shaanxi, China.
Jianhui LiAir force medical center, PLA, Beijing, 100142, China.
Xin WangDepartment of Gastroenterology, Tangdu Hospital, Air Force Military Medical University, Xi'an, 710038, Shaanxi, China.
Jing MaDepartment of Gastroenterology, Tangdu Hospital, Air Force Military Medical University, Xi'an, 710038, Shaanxi, China. majing1128fmmu@163.com.

Funding

National Natural Science Foundation of China 82341223the Youth Science Foundation of NSFC 82202844
6 · The paper itself

Abstract

objectiveUlcerative colitis (UC) and Hashimoto's thyroiditis frequently cooccur in patients with multiple autoimmune conditions, but the specific association between UC and hypothyroidism is unknown. We used Mendelian randomization (MR) methods to determine the causal relationship between UC and hypothyroidism.

methodsWe obtained single nucleotide polymorphisms (SNPs) related to ulcerative colitis (UC) and hypothyroidism from genome-wide association studies (GWAS) available in the public database of the Integrated Epidemiology Unit (IEU). To assess the causal relationship between UC and hypothyroidism, we employed MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode methods. Sensitivity analyses were performed using Cochran's Q test, the horizontal pleiotropy test, and the leave-one-out (LOO) method to assess the reliability of the MR data. The genes corresponding to instrumental variables (IVs) were subjected to Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of the Genome (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) analysis to explore the mechanisms behind the causal relationships at the gene level.

resultsForward MR analysis indicated that hypothyroidism was associated with an increased risk of UC (IVW: P = 0.02, OR = 9.71, 95% confidence interval (CI) = 1.36-69.46). In contrast, reverse MR did not demonstrate a causal relationship between UC and hypothyroidism (IVW: P = 0.53). Sensitivity analysis proved the reliability of the results. The PPI network revealed CD247, CD80, and STAT4 as central genes. GO and KEGG analyses revealed significant enrichment of the T cell, gamma interferon (IFN-γ), and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways.

conclusionHypothyroidism was a risk factor for UC. The balance of T-cell differentiation played an important role in the process of hypothyroidism-induced UC, and IL-21 might be the key to finding a cure. Enrichment of PD-1/PD-L1 might attenuate inflammation by suppressing the immune action of T cells.

Indexed as

Colitis, UlcerativeGenome-Wide Association StudyHypothyroidismMendelian Randomization AnalysisPolymorphism, Single NucleotideCausalityGenetic Predisposition to DiseaseHumansSTAT4 Transcription FactorSTAT4 protein, humanSTAT4 Transcription FactorCausal relationshipHypothyroidismMendelian randomizationUlcerative colitis

Identifiers

PMID39478467
PMCPMC11526713

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.