Department of Dermatology and Venerology, Peking University First Hospital, Beijing, China.
Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, Peking University First Hospital, Beijing, China.
Front Immunol. 2024 Mar 13;15:1365118. doi: 10.3389/fimmu.2024.1365118. eCollection 2024.
The association between psoriasis vulgaris and bullous pemphigoid (BP) remains largely unknown.
To investigate whether there is a causal effect between psoriasis vulgaris and BP.
Two-sample bidirectional Mendelian randomization (MR) analyses were conducted using publicly released genome-wide association studies (GWAS) summary statistics. The GWAS summary statistics for BP were downloaded online from FinnGen Biobank Documentation of the R12 release, which includes 219 BP cases and 218,066 controls. The GWAS data for psoriasis vulgaris were extracted from Sakaue et al., which comprises 5072 cases and 478,102 controls. Single-nucleotide polymorphisms (SNPs) associated with exposure were selected as instrumental variables by performing additional quality control steps. The inverse-variance-weighted (IVW) method was used for the primary MR analyses, and the MR-Egger regression, weighted mode method, weighted median method, and simple mode were employed for sensitivity analyses. The MR-Egger intercept test and "leave-one-out" sensitivity analysis were performed to evaluate the horizontal pleiotropy and the potentially influential SNPs, respectively.
Genetically determined log odds of psoriasis vulgaris were associated with an increased risk of BP (IVW: odds ratio (OR) = 1.263, 95% confidence interval (CI): 1.013-1.575, =0.038). Sensitivity analyses by the weighted mode (OR=1.255, 95%CI: 0.973-1.618, =0.106), MR Egger (OR=1.315, 95%CI: 0.951-1.817, =0.126), simple mode (OR=1.414, 95%CI: 0.823-2.429, =0.234) and weighted median method (OR=1.177, 95%CI: 0.889-1.559, =0.254) derived directionally consistent relationship between the genetically predicted log odds of psoriasis vulgaris and risks of developing BP. On the contrary, we found that genetically predicted BP had no significant effect on psoriasis vulgaris (IVW: OR=0.996, = 0.707), indicating the unidirectionality of the relationship. MR-Egger intercept tests showed no evidence of horizontal pleiotropy. No influential SNP driving the results was detected by the leave-one-out sensitivity analysis.
Our results suggested that psoriasis vulgaris causally increases the risk of BP, highlighting the need for potential strategies for the prevention and early diagnosis of comorbid BP in patients with psoriasis vulgaris. Further researches into this association and underlying mechanisms are warranted.
寻常型银屑病与大疱性类天疱疮（BP）之间的关联仍知之甚少。
探讨寻常型银屑病与 BP 之间是否存在因果关系。
采用两样本双向孟德尔随机化（MR）分析，使用公开发布的全基因组关联研究（GWAS）汇总统计数据。BP 的 GWAS 汇总统计数据从 FinnGen 生物银行 R12 版本的文档中在线下载，其中包括 219 例 BP 病例和 218066 例对照。寻常型银屑病的 GWAS 数据从 Sakaue 等人的研究中提取，该研究包括 5072 例病例和 478102 例对照。通过进行额外的质量控制步骤，选择与暴露相关的单核苷酸多态性（SNP）作为工具变量。采用逆方差加权（IVW）法进行主要 MR 分析，并采用 MR-Egger 回归、加权中位数法、加权模式法和简单模式法进行敏感性分析。MR-Egger 截距检验和“逐一剔除”敏感性分析分别用于评估水平异质性和潜在的有影响的 SNP。
遗传决定的寻常型银屑病对数优势与 BP 风险增加相关（IVW：比值比（OR）=1.263，95%置信区间（CI）：1.013-1.575，=0.038）。加权中位数法（OR=1.177，95%CI：0.889-1.559，=0.254）和简单模式法（OR=1.414，95%CI：0.823-2.429，=0.234）、MR Egger（OR=1.315，95%CI：0.951-1.817，=0.126）和加权模式法（OR=1.255，95%CI：0.973-1.618，=0.106）的加权模式、MR Egger（OR=1.315，95%CI：0.951-1.817，=0.126）和简单模式（OR=1.414，95%CI：0.823-2.429，=0.234）的敏感性分析得出了寻常型银屑病遗传预测对数优势与 BP 发病风险之间存在一致的方向关系。相反，我们发现遗传预测的 BP 对寻常型银屑病没有显著影响（IVW：OR=0.996，=0.707），表明这种关系具有单向性。MR-Egger 截距检验显示不存在水平异质性的证据。通过逐一剔除敏感性分析未发现驱动结果的有影响的 SNP。
我们的研究结果表明，寻常型银屑病可使 BP 的发病风险增加，这突出表明需要针对寻常型银屑病患者潜在的 BP 共病制定预防和早期诊断策略。有必要进一步研究这种关联及其潜在机制。
