白癜风与自身免疫性甲状腺疾病之间的因果关系：双向两样本 Mendelian 随机分析。

The causal relationship between vitiligo and autoimmune thyroid diseases: A bidirectional two-sample Mendelian randomization analysis.

机构信息

Department of Dermatology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.

Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Skin Res Technol. 2024 Jun;30(6):e13742. doi: 10.1111/srt.13742.

DOI:10.1111/srt.13742

PMID:38807429

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11133963/

Abstract

BACKGROUND

Vitiligo is an acquired autoimmune depigmented disorder characterized by the presence of white and well-defined patches on the skin, mucous membrane, or both. It is associated with a significant disease burden and has a profoundly impacts patients' quality of life. Autoimmune thyroid diseases (AITDs) result from an autoimmune system dysregulation, leading to an erroneous immune attack on the thyroid gland. Previous observational and epidemiological studies have suggested the association between vitiligo and AITDs. However, the bidirectional cause-effect relationship between vitiligo and AITDs has not been formally assessed.

METHOD

Two-sample bidirectional Mendelian randomization (MR) analysis was conducted to explore potential causal relationships between genetically increased risk of vitiligo and AITDs, using summary statistics from genome-wide association studies in European populations. Causal effects were primarily estimated using the inverse variance weighted method, and additional quality control was performed using the MR-Egger, weighted median, simple mode, and weight mode methods. Sensitivity analysis was conducted to assess the robustness of the results.

RESULTS

The forward MR analysis showed a positive causal relationship between vitiligo and autoimmune thyroiditis (AIT), autoimmune hyperthyroidism (AIH), and Graves' disease (GD). The odds ratio (OR) were 1.17 (95% CI, 1.01-1.35; p = 0.04), 1.12 (95% CI, 1.03-1.22; p = 0.01), and 1.13 (95% CI, 1.06-1.20; p < 0.01), respectively. In the reverse MR analysis, a positive causal relationship was found between AIT and vitiligo, with an OR of 1.10 (95% CI, 1.01-1.35; p = 0.04). However, no causal relationship was observed between AIH (p = 0.10) or GD (p = 0.61) and vitiligo. Sensitivity analysis revealed no evidence of horizontal pleiotropy or heterogeneity.

CONCLUSIONS

The genetic-level investigation provides evidence of a genetic causal association between susceptibility to vitiligo and an increased risk of AITDs. Additionally, the results demonstrate a genetic causal association between susceptibility to AIT and an increased risk of vitiligo, while not indicating a similar association with susceptibility to AIH or GD.

摘要

背景

白癜风是一种获得性自身免疫性脱色素疾病，其特征是皮肤、黏膜或两者上存在白色且界限分明的斑块。它与显著的疾病负担有关，并对患者的生活质量产生深远影响。自身免疫性甲状腺疾病（AITD）是由于自身免疫系统失调导致的，从而导致对甲状腺的错误免疫攻击。先前的观察性和流行病学研究表明了白癜风与 AITD 之间的关联。然而，白癜风和 AITD 之间的双向因果关系尚未得到正式评估。

方法

采用两样本双向孟德尔随机化（MR）分析，使用欧洲人群全基因组关联研究的汇总统计数据，探讨遗传上增加的白癜风风险与 AITD 之间的潜在因果关系。主要使用逆方差加权法估计因果效应，并使用 MR-Egger、加权中位数、简单模式和加权模式方法进行额外的质量控制。进行敏感性分析以评估结果的稳健性。

结果

正向 MR 分析显示白癜风与自身免疫性甲状腺炎（AIT）、自身免疫性甲状腺功能亢进症（AIH）和格雷夫斯病（GD）之间存在正相关的因果关系。比值比（OR）分别为 1.17（95%置信区间，1.01-1.35；p=0.04）、1.12（95%置信区间，1.03-1.22；p=0.01）和 1.13（95%置信区间，1.06-1.20；p<0.01）。在反向 MR 分析中，发现 AIT 与白癜风之间存在正相关的因果关系，OR 为 1.10（95%置信区间，1.01-1.35；p=0.04）。然而，AIH（p=0.10）或 GD（p=0.61）与白癜风之间没有因果关系。敏感性分析未发现水平遗传异质性或异质性的证据。