Dataset Information

Mendelian randomization study highlights hypothyroidism as a causal determinant of alopecia areata.

ABSTRACT:

Background

Although observational studies have found an association between hypothyroidism and alopecia areata, the causality of this relationship remains unclear.

Objectives

This study aimed to investigate the genetic variants associated with hypothyroidism and their potential impact on the risk of developing alopecia areata.

Methods

genome-wide association study summary statistics for hypothyroidism (30,155 cases and 379,986 controls) and alopecia areata (289 cases and 211,139 controls) were obtained from the IEU OpenGwas project. The inverse variance-weighted method was used as the primary analysis method to evaluate the causality between hypothyroidism and alopecia areata, supplemented by the weighted median, MR-Egger, simple mode and weighted mode. Furthermore, the function of causal SNPs was evaluated by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction networks.

Result

Utilizing two-sample Mendelian randomization analysis, we found that the single-nucleotide polymorphisms (SNPs) of hypothyroidism (OR = 1.40, 95% CI: 1.12-1.75, p = 3.03×10^-3) significantly increased the risk of alopecia areata ( 289 cases and 211,139 controls ). KEGG pathway analysis showed that the candidate genes were mainly enriched in virion-herpesvirus, Th1 and Th2 cell differentiation, Th17 cell differentiation, T-cell receptor signaling pathway, PD-L1/PD-1 checkpoint pathway in cancer and Toll-like receptor signaling pathway. Protein-protein interaction networks results showed that CTLA4, STAT4, IL2RA, TYK2, IRF7, SH2B3, BACH2, TLR3, NOD2, and FLT3.

Conclusion

This study provided compelling genetic evidence supporting a causative association between hypothyroidism and alopecia areata, which could potentially inform the development of more efficacious treatment strategies for patients afflicted by alopecia areata.

SUBMITTER: Zheng XY

PROVIDER: S-EPMC10826415 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Mendelian randomization study highlights hypothyroidism as a causal determinant of alopecia areata.

Zheng Xue-Yong XY Ma Yan-Ping YP Zhang Bo B Chen Yan-Xin YX Tang Lei L Tai Xiao-Hua XH Cao Jia-Hao JH

Frontiers in endocrinology 20240116

<h4>Background</h4>Although observational studies have found an association between hypothyroidism and alopecia areata, the causality of this relationship remains unclear.<h4>Objectives</h4>This study aimed to investigate the genetic variants associated with hypothyroidism and their potential impact on the risk of developing alopecia areata.<h4>Methods</h4>genome-wide association study summary statistics for hypothyroidism (30,155 cases and 379,986 controls) and alopecia areata (289 cases and 21 ...[more]

PMID: 38292771

Similar Datasets

Project description: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.

Dataset Information

Mendelian randomization study highlights hypothyroidism as a causal determinant of alopecia areata.

Background

Objectives

Methods

Result

Conclusion

Publications

Mendelian randomization study highlights hypothyroidism as a causal determinant of alopecia areata.

Similar Datasets

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