Department of Dermatology and Venereology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China.
Department of Clinical Epidemiology Research Center, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China.
Skin Res Technol. 2024 Jul;30(7):e13795. doi: 10.1111/srt.13795.
This study is designed to explore the potential causal relationship between psoriasis and psoriatic arthritis (PsA) while investigating the genetic basis shared by these inflammatory diseases.
Significant single nucleotide polymorphisms (SNPs) associated with UC, psoriasis, and PsA were selected as genetic instrumental variables using Genome-Wide Association Study (GWAS) datasets. Additionally, Mendelian randomization (MR) methods, including inverse-variance weighting (IVW), MR-Egger regression, and Weighted Median (WME), were utilized to evaluate the causal relationships between these diseases. Moreover, sensitivity analysis and heterogeneity testing were conducted to validate the stability of the results.
A total of 123 significant SNPs associated with psoriasis, PsA, and UC were identified as genetic instrumental variables based on GWAS datasets. The analysis revealed a 36% increased risk of UC with psoriasis (odds ratio [OR] = 1.350, 95% confidence interval [CI] = 1.065-1.729, P = 0.012) and a 32.9% increased risk of UC with PsA (OR = 1.329, 95% CI = 1.176-1.592, P < 0.001). Further analysis showed a 43.5% increased risk of psoriasis with UC (OR = 1.435, 95% CI = 1.274-1.831, P < 0.001) and a 45.8% increased risk of PsA with UC (OR = 1.458, 95% CI = 1.166-1.822, P = 0.0013). In addition, sensitivity analysis and heterogeneity testing demonstrated the high stability of these results. Particularly, neither MR-Egger regression analysis nor leave-one-out analysis revealed significant heterogeneity or pleiotropy bias, indicating the reliability of these causal estimates. Moreover, the use of the MR-PRESSO further confirmed the positive correlation between psoriasis and UC, and the corrected estimates remained consistent with IVW analysis results after excluding potential outlier SNPs, enhancing the credibility of the analysis.
This study strengthens the understanding of the genetic and causal relationships among UC, psoriasis, and PsA through GWAS and MR methods, revealing the genetic basis they may share. These findings not only provide a novel perspective on the comorbidity mechanisms of these diseases but also offer a valuable reference for the development of future treatment strategies and intervention measures.
本研究旨在探讨银屑病和银屑病关节炎（PsA）之间潜在的因果关系，同时研究这些炎症性疾病之间共享的遗传基础。
使用全基因组关联研究（GWAS）数据集，选择与 UC、银屑病和 PsA 相关的显著单核苷酸多态性（SNP）作为遗传工具变量。此外，采用逆方差加权（IVW）、MR-Egger 回归和加权中位数（WME）等孟德尔随机化（MR）方法来评估这些疾病之间的因果关系。此外，还进行了敏感性分析和异质性检验，以验证结果的稳定性。
根据 GWAS 数据集，共确定了 123 个与银屑病、PsA 和 UC 相关的显著 SNP，作为遗传工具变量。分析结果显示，银屑病患者患 UC 的风险增加了 36%（比值比[OR] = 1.350，95%置信区间[CI] = 1.065-1.729，P = 0.012），PsA 患者患 UC 的风险增加了 32.9%（OR = 1.329，95% CI = 1.176-1.592，P < 0.001）。进一步分析显示，UC 患者患银屑病的风险增加了 43.5%（OR = 1.435，95% CI = 1.274-1.831，P < 0.001），UC 患者患 PsA 的风险增加了 45.8%（OR = 1.458，95% CI = 1.166-1.822，P = 0.0013）。此外，敏感性分析和异质性检验表明这些结果具有较高的稳定性。特别是，MR-Egger 回归分析和单倍型不平衡检验均未显示出显著的异质性或多效性偏倚，表明这些因果估计的可靠性。此外，使用 MR-PRESSO 进一步证实了银屑病和 UC 之间的正相关关系，并且在排除潜在的异常值 SNP 后，校正后的估计值与 IVW 分析结果一致，增强了分析的可信度。
本研究通过 GWAS 和 MR 方法，加强了对 UC、银屑病和 PsA 之间遗传和因果关系的理解，揭示了它们可能共享的遗传基础。这些发现不仅为这些疾病的共病机制提供了新的视角，也为未来治疗策略和干预措施的制定提供了有价值的参考。
