Cong Xianzhu, Li Shuang, Ge Jiayu, Zhu Yuhang, Qi Xuejie, Shi Fuyan, Wang Suzhen
Department of Health Statistics, School of Public Health, Shandong Second Medical University, Weifang, Shandong, China.
Medicine (Baltimore). 2025 Sep 5;104(36):e43426. doi: 10.1097/MD.0000000000043426.
Both psoriasis and autoimmune thyroid diseases are characterized by chronic inflammation. The previous studies indicated a potential association between psoriasis and autoimmune thyroid diseases. However, the direction and nature of these relationships remain unclear. This study aimed to investigate the bidirectional causal relationships between multiple thyroid diseases (hypothyroidism, hyperthyroidism, Hashimoto thyroiditis, and Graves disease (GD)) and psoriasis (PsO) as well as its subtypes (psoriasis vulgaris (PV) and psoriatic arthritis (PsA)) through a two-sample Mendelian randomization (MR) approach. A bidirectional, two-sample MR analysis was conducted using genome-wide association study (GWAS) summary statistics from large European populations. Independent single nucleotide polymorphisms (SNPs) associated with thyroid diseases and psoriasis were selected as instrumental variables. The MR-PRESSO method was applied in 2 rounds to identify and remove outlier SNPs. MR-Egger regression, inverse-variance weighted (IVW), and weighted median methods were employed to assess causal relationships. This study provides genetic evidence of a suggestive association between hypothyroidism, the most common form of thyroid disease, and an increased risk of developing PsO (odds ratio (OR) = 1.059, P = .038). Additionally, genetic predisposition to hypothyroidism was significantly associated with its subtype, PsA (OR = 1.184, P = 2.40 × 10-5). In the inverse MR analyses, PV, the primary subtype of PsO, was suggestively associated with an increased risk of GD (OR = 1.113, P = .002) and hyperthyroidism (OR = 1.053, P = .040). However, it was associated with a decreased risk of hypothyroidism (OR = 0.977, P = .025). This study presents evidence supporting bidirectional causal relationships between thyroid diseases and psoriasis. These findings offer new insights into shared inflammatory pathways that may underlie these comorbidities.
银屑病和自身免疫性甲状腺疾病均以慢性炎症为特征。既往研究表明银屑病与自身免疫性甲状腺疾病之间存在潜在关联。然而,这些关系的方向和性质仍不明确。本研究旨在通过两样本孟德尔随机化(MR)方法,探究多种甲状腺疾病(甲状腺功能减退症、甲状腺功能亢进症、桥本甲状腺炎和格雷夫斯病(GD))与银屑病(PsO)及其亚型(寻常型银屑病(PV)和银屑病关节炎(PsA))之间的双向因果关系。使用来自欧洲大型人群的全基因组关联研究(GWAS)汇总统计数据进行双向两样本MR分析。选择与甲状腺疾病和银屑病相关的独立单核苷酸多态性(SNP)作为工具变量。MR-PRESSO方法分两轮应用,以识别和去除异常SNP。采用MR-Egger回归、逆方差加权(IVW)和加权中位数方法评估因果关系。本研究提供了遗传证据,表明最常见的甲状腺疾病形式甲状腺功能减退症与发生PsO的风险增加之间存在提示性关联(优势比(OR)=1.059,P=0.038)。此外,甲状腺功能减退症的遗传易感性与其亚型PsA显著相关(OR=1.184,P=2.40×10⁻⁵)。在反向MR分析中,PsO的主要亚型PV与GD风险增加(OR=1.113,P=0.002)和甲状腺功能亢进症(OR=1.053,P=0.040)存在提示性关联。然而,它与甲状腺功能减退症风险降低相关(OR=0.977,P=0.025)。本研究提供了支持甲状腺疾病与银屑病之间双向因果关系的证据。这些发现为可能是这些合并症基础的共同炎症途径提供了新见解。