Xu Shuqin, Liu Long, Li Chentao, Ren Yaoxing, Zhang Miaomiao, Xiang Linbiao, Li Nan, Xu Jiaru, Bai Shuang, Lv Yi
Department of hepatobiliary surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Int J Med Sci. 2025 Jan 1;22(1):121-131. doi: 10.7150/ijms.102369. eCollection 2025.
The aim of this study is to utilize two-sample Mendelian randomization (MR) to investigate the potential causal relationship among psoriasis, iridocyclitis, and non-alcoholic fatty liver disease (NAFLD), and to explore any potential mediation effects. Pooled data were derived from the public genome-wide association study (GWAS) in NAFLD (finn-b-NAFLD), iridocyclitis (finn-b-H7_IRIDOCYCLITIS) and psoriasis (finn-b-L12_PSORI_VULG). Univariable MR (UVMR) analysis was implemented to explore the causal relationship among psoriasis, iridocyclitis, and NAFLD, and inverse variance weighting (IVW) was used as the primary analytical method. Additionally, Cochran's Q and MR-Egger tests were utilized to evaluate the heterogeneity and horizontal pleiotropy, respectively. Simultaneously, the reliability of MR results was evaluated by leave-one-out (LOO) method. Finally, multivariable MR (MVMR) analysis and mediation analysis were performed to further reveal the mechanism of mediation effect among the three diseases. With regard to the results of IVW method, both iridocyclitis (=0.0185, OR=1.0757) and psoriasis (=0.0115, OR=1.1246) had significant causal relationships with the occurrence of NAFLD, and both were risk factors for NAFLD. Besides, it was observed that there was significant causal effect of iridocyclitis (= 0.0181, OR=1.1729) on psoriasis and iridocyclitis was a risk factor. Additionally, there was a lack of heterogeneity (>0.05) among the selected SNPs when MR analysis was conducted with NAFLD as the outcome. Horizontal pleiotropy was not detected by the MR-Egger test. The LOO analysis demonstrated that the instrumental variables were appropriately chosen, suggesting the reliability of the MR results. Ultimately, MVMR and mediation analysis revealed iridocyclitis affected the development of NAFLD, 20.81% of which was caused by the pathway of iridocyclitis induced psoriasis leading to NAFLD. This study highlighted that iridocyclitis was significantly associated with an increased risk of NAFLD and that psoriasis was involved in the mechanism by which iridocyclitis triggered NAFLD, which might offer potential preventive strategies for NAFLD.
本研究旨在利用两样本孟德尔随机化（MR）方法，探讨银屑病、虹膜睫状体炎和非酒精性脂肪性肝病（NAFLD）之间潜在的因果关系，并探索任何潜在的中介效应。汇总数据来自公开的NAFLD全基因组关联研究（GWAS）（finn-b-NAFLD）、虹膜睫状体炎（finn-b-H7_IRIDOCYCLITIS）和银屑病（finn-b-L12_PSORI_VULG）。采用单变量MR（UVMR）分析来探讨银屑病、虹膜睫状体炎和NAFLD之间的因果关系，并将逆方差加权（IVW）作为主要分析方法。此外，分别利用Cochran's Q检验和MR-Egger检验来评估异质性和水平多效性。同时，采用留一法（LOO）评估MR结果的可靠性。最后，进行多变量MR（MVMR）分析和中介分析，以进一步揭示三种疾病之间中介效应的机制。关于IVW方法的结果，虹膜睫状体炎（=0.0185，OR=1.0757）和银屑病（=0.0115，OR=1.1246）与NAFLD的发生均存在显著因果关系，二者均为NAFLD的危险因素。此外，观察到虹膜睫状体炎（=0.0181，OR=1.1729）对银屑病有显著因果效应，虹膜睫状体炎是一个危险因素。此外，以NAFLD为结局进行MR分析时，所选单核苷酸多态性（SNP）之间不存在异质性（>0.05）。MR-Egger检验未检测到水平多效性。LOO分析表明工具变量选择恰当，提示MR结果可靠。最终，MVMR和中介分析显示虹膜睫状体炎影响NAFLD的发生发展，其中20.81%是由虹膜睫状体炎诱发银屑病进而导致NAFLD的途径所致。本研究强调虹膜睫状体炎与NAFLD风险增加显著相关，且银屑病参与了虹膜睫状体炎引发NAFLD的机制，这可能为NAFLD提供潜在的预防策略。
