Zhang Fang, Li Jie, Zhao Diqian, Bai Wenzhe
Department of Dermatology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 16369 Jingshi Road, Jinan, Shandong Province, China.
Clin Rheumatol. 2025 May 29. doi: 10.1007/s10067-025-07508-7.
Psoriatic arthritis (PsA) is an immune-mediated chronic inflammatory disease that causes chronic pain, psychological problems, and a significant economic burden, and therefore must be diagnosed and treated early. Existing treatments have limited efficacy and side effects. The study aimed to identify potential drug targets associated with psoriatic arthritis through proteomics and Mendelian randomization (MR) analysis.
Large-scale genome-wide association studies and proteomics data were used to assess the causal relationship between plasma proteins and PsA through MR analysis, Bayesian colocalization analysis, summary data-based Mendelian randomization (SMR) analysis, and heterogeneity in dependent instruments (HEIDI) test, and to analyze protein-protein interaction networks.
The study identified 26 proteins that may be causally related to PsA, of which 15 were positively correlated and 11 negatively correlated. According to the results of SMR analysis and colocalization analysis, these targets were further analyzed and classified into high, medium, and low confidence levels. High confidence targets include APOF, PRSS27, and DDX58, which were consistently supported by multiple analyses.
The study identified several promising targets for the treatment of psoriatic arthritis through multiple analysis methods, providing a theoretical basis for future treatment strategies, but further experimental verification and clinical research are needed. Key Points • Using large-scale genome-wide association studies and proteomics data, drug targets for psoriatic arthritis (PsA) were identified through Mendelian randomization analysis, Bayesian colocalization analysis, and summary-data-based Mendelian randomization (SMR) analysis. • The study identified 26 proteins that are causally related to psoriatic arthritis, of which 15 are positively and 11 are negatively associated with psoriatic arthritis. • Among the identified proteins, APOF, PRSS27, and DDX58 were ranked as high confidence targets.
银屑病关节炎（PsA）是一种免疫介导的慢性炎症性疾病，会导致慢性疼痛、心理问题和巨大的经济负担，因此必须尽早诊断和治疗。现有治疗方法疗效有限且有副作用。本研究旨在通过蛋白质组学和孟德尔随机化（MR）分析确定与银屑病关节炎相关的潜在药物靶点。
利用大规模全基因组关联研究和蛋白质组学数据，通过MR分析、贝叶斯共定位分析、基于汇总数据的孟德尔随机化（SMR）分析和依赖工具异质性（HEIDI）检验评估血浆蛋白与PsA之间的因果关系，并分析蛋白质-蛋白质相互作用网络。
该研究确定了26种可能与PsA存在因果关系的蛋白质，其中15种呈正相关，11种呈负相关。根据SMR分析和共定位分析结果，对这些靶点进一步分析并分为高、中、低置信度水平。高置信度靶点包括APOF、PRSS27和DDX58，多种分析均一致支持这些靶点。
本研究通过多种分析方法确定了几个有前景的银屑病关节炎治疗靶点，为未来治疗策略提供了理论依据，但仍需要进一步的实验验证和临床研究。要点 • 利用大规模全基因组关联研究和蛋白质组学数据，通过孟德尔随机化分析、贝叶斯共定位分析和基于汇总数据的孟德尔随机化（SMR）分析确定了银屑病关节炎（PsA）的药物靶点。 • 该研究确定了26种与银屑病关节炎存在因果关系的蛋白质，其中15种与银屑病关节炎呈正相关，11种呈负相关。 • 在确定的蛋白质中，APOF、PRSS27和DDX58被列为高置信度靶点。
