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

Xue-Yong Zheng; Yan-Ping Ma; Bo Zhang; Yan-Xin Chen; Lei Tang; Xiao-Hua Tai; Jia-Hao Cao

doi:10.3389/fendo.2023.1309620

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

Front Endocrinol (Lausanne). 2024 Jan 16:14:1309620. doi: 10.3389/fendo.2023.1309620. eCollection 2023.

Authors

Xue-Yong Zheng^#¹, Yan-Ping Ma^#², Bo Zhang¹, Yan-Xin Chen¹, Lei Tang¹, Xiao-Hua Tai¹, Jia-Hao Cao¹

Affiliations

¹ Department of Thyroid Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.
² Department of Endoscopic Center, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.

^# Contributed equally.

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.

Keywords: GWAS summary statistics; SNPs; alopecia areata; hypothyroidism; two-sample Mendelian randomization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alopecia Areata* / genetics
Genome-Wide Association Study
Humans
Hypothyroidism* / complications
Hypothyroidism* / genetics
Mendelian Randomization Analysis

Supplementary concepts

Diffuse alopecia

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Science and Technology Program of Jia Xing (grant numbers 2021AD30085).