Integrative Mendelian Randomization and Transcriptomic Analysis Reveal the Causal Association between Psoriatic...

Psoriatic arthritis (PsA) is a chronic inflammatory condition often associated with uveitis in clinical practice. However, the causal relationship between these diseases and their underlying mechanisms of interaction remain unclear. Therefore, our objective was to investigate the cause-effect relationships between PsA and uveitis and explore the association between the 2 diseases. The MR analysis revealed an OR of 1.90 (95% confidence interval = 1.33-2.70), indicating a significant association between PsA and increased uveitis risk. Validation analyses confirmed the robustness of the MR findings. A total of 33 colocalized genes were identified, and 4 key genes-BAK1, FKBPL, HLA-DQB1, and ZKSCAN4-were selected by intersecting colocalized genes with 1681 differentially expressed genes. A nomogram based on these genes demonstrated strong predictive ability. Functional enrichment analyses highlighted their involvement in critical biological processes, with HLA-DQB1 and immune cells, particularly eosinophils and neutrophils, identified as significant risk factors for uveitis. In conclusion, this study establishes a causal link between PsA and uveitis and identifies 4 key genes-BAK1, FKBPL, HLA-DQB1, and ZKSCAN4-that may contribute to the shared pathogenesis of these diseases. These findings provide mechanistic insights into PsA-uveitis comorbidity and potential therapeutic targets for clinical management.