银屑病与非酒精性脂肪性肝病之间因果关系：双向双样本孟德尔随机化研究

Causal Relationship between Psoriasis and Non-Alcoholic Fatty Liver Disease: A Bidirectional Two-Sample Mendelian Randomization Study

摘要: 目的：采用孟德尔随机化(MR)研究银屑病与非酒精性脂肪性肝病之间的双向因果关系。方法：我们使用来自银屑病和NAFLD的汇总GWAS数据进行了双样本孟德尔随机化(TSMR)分析。选择满足孟德尔随机化三个核心假设的工具变量(IV)。TSMR分析采用逆方差加权(IVW)法为主要分析方法进行分析，辅以MR-Egger回归法和加权中位数(WM)法进行。为确保研究结果的准确性和稳定性，进行了异质性检验、多重有效性检验和敏感性分析。结果：IVW方法提示银屑病与非酒精性脂肪性肝病之间有因果关系(OR 1.20；95%可信区间：1.10~1.32；P = 9.58 × 10⁻⁵)。MR-Egger回归未显示有水平多效性。Cochran-Q检验结果表明纳入分析的SNP之间不存在异质性，MR-PRESS0检验未发现离群的SNP，“留一法”敏感性分析显示，因果估计不太可能受到某些SNP效应的影响，反向MR分析的结果表明非酒精性脂肪性肝病增加银屑病患病率。结论：银屑病与非酒精性脂肪性肝病之间存在因果关系。

Abstract: Objective: Mendelian randomization (MR) was used to investigate the bidirectional causal relationship between psoriasis and non-alcoholic fatty liver disease (NAFLD). Method: We performed a two-sample Mendelian randomization (TSMR) analysis using pooled GWAS data from psoriasis and NAFLD. Instrumental variables (IVs) were selected to satisfy the three core assumptions of Mendelian randomization. TSMR analyses were performed using the inverse variance weighting (IVW) method as the primary analytical method for the analyses, supplemented by MR-Egger regression and weighted median (WM) methods. Heterogeneity test, multiple validity test and sensitivity analysis were conducted to ensure the accuracy and stability of the findings. Results: The IVW method suggested a causal association between psoriasis and non-alcoholic fatty liver disease (OR 1.20; 95% confidence interval: 1.10~1.32; P = 9.58 × 10⁻⁵). MR-Egger regression did not show horizontal pleiotropy. The results of Cochran’s Q-test showed no heterogeneity between the SNPs included in the analysis, MR-PRESSO found no outlier SNPs, leave-one-out sensitivity analyses showed that causal estimates were unlikely to be affected by certain SNP effects, and the results of inverse MR analyses showed that NAFLD increased the prevalence of psoriasis. Conclusion: There is a causal relationship between psoriasis and non-alcoholic fatty liver disease.