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Abstract：
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, P=0.038). Sensitivity analyses by the weighted mode (OR=1.255, 95%CI: 0.973-1.618, P=0.106), MR Egger (OR=1.315, 95%CI: 0.951-1.817, P=0.126), simple mode (OR=1.414, 95%CI: 0.823-2.429, P=0.234) and weighted median method (OR=1.177, 95%CI: 0.889-1.559, P=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, P= 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.
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, P=0.038). Sensitivity analyses by the weighted mode (OR=1.255, 95%CI: 0.973-1.618, P=0.106), MR Egger (OR=1.315, 95%CI: 0.951-1.817, P=0.126), simple mode (OR=1.414, 95%CI: 0.823-2.429, P=0.234) and weighted median method (OR=1.177, 95%CI: 0.889-1.559, P=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, P= 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.
摘要：
■寻常型银屑病与大疱性类天疱疮（BP）之间的关联在很大程度上仍然未知。
■调查寻常型银屑病与BP之间是否存在因果关系。
■使用公开发布的全基因组关联研究（GWAS）汇总统计进行双样本双向孟德尔随机化（MR）分析。BP的GWAS汇总统计数据是从R12版本的FinnGenBiobank文档在线下载的，其中包括219例BP病例和218,066例对照。寻常型银屑病的GWAS数据来自Sakaue等人。,其中包括5072例病例和478,102例对照。通过执行其他质量控制步骤，选择与暴露相关的单核苷酸多态性（SNP）作为辅助变量。逆方差加权(IVW)方法用于主要的MR分析，和MR-Egger回归，加权模式法，加权中位数法，采用简单模式进行敏感性分析。进行了MR-Egger截距检验和“留一”敏感性分析，以评估水平多效性和潜在影响的SNP，分别。
■遗传确定的寻常型银屑病对数几率与BP风险增加相关（IVW：比值比（OR）=1.263，95％置信区间（CI）：1.013-1.575，P=0.038）。加权模式敏感性分析(OR=1.255,95CI:0.973-1.618,P=0.106),MREgger（OR=1.315，95CI：0.951-1.817，P=0.126），简单模式(OR=1.414,95CI:0.823-2.429,P=0.234)和加权中位数法(OR=1.177,95CI:0.889-1.559,P=0.254)得出寻常型银屑病遗传预测对数几率与发生BP风险之间的方向一致关系.相反,我们发现遗传预测的BP对寻常型银屑病无显著影响(IVW:OR=0.996,P=0.707),表示关系的单向性。MR-Egger截距测试表明没有水平多效性的证据。留一敏感性分析未检测到有影响的SNP驱动结果。
■我们的研究结果表明，寻常型银屑病会增加血压的风险，强调寻常型银屑病合并BP的预防和早期诊断的潜在策略的必要性。有必要对这种关联和潜在机制进行进一步研究。
■调查寻常型银屑病与BP之间是否存在因果关系。
■使用公开发布的全基因组关联研究（GWAS）汇总统计进行双样本双向孟德尔随机化（MR）分析。BP的GWAS汇总统计数据是从R12版本的FinnGenBiobank文档在线下载的，其中包括219例BP病例和218,066例对照。寻常型银屑病的GWAS数据来自Sakaue等人。,其中包括5072例病例和478,102例对照。通过执行其他质量控制步骤，选择与暴露相关的单核苷酸多态性（SNP）作为辅助变量。逆方差加权(IVW)方法用于主要的MR分析，和MR-Egger回归，加权模式法，加权中位数法，采用简单模式进行敏感性分析。进行了MR-Egger截距检验和“留一”敏感性分析，以评估水平多效性和潜在影响的SNP，分别。
■遗传确定的寻常型银屑病对数几率与BP风险增加相关（IVW：比值比（OR）=1.263，95％置信区间（CI）：1.013-1.575，P=0.038）。加权模式敏感性分析(OR=1.255,95CI:0.973-1.618,P=0.106),MREgger（OR=1.315，95CI：0.951-1.817，P=0.126），简单模式(OR=1.414,95CI:0.823-2.429,P=0.234)和加权中位数法(OR=1.177,95CI:0.889-1.559,P=0.254)得出寻常型银屑病遗传预测对数几率与发生BP风险之间的方向一致关系.相反,我们发现遗传预测的BP对寻常型银屑病无显著影响(IVW:OR=0.996,P=0.707),表示关系的单向性。MR-Egger截距测试表明没有水平多效性的证据。留一敏感性分析未检测到有影响的SNP驱动结果。
■我们的研究结果表明，寻常型银屑病会增加血压的风险，强调寻常型银屑病合并BP的预防和早期诊断的潜在策略的必要性。有必要对这种关联和潜在机制进行进一步研究。
