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

Area of Science:

• Rheumatology
• Ophthalmology
• Genetics

Background:

• Psoriatic arthritis (PsA) is a chronic inflammatory disease frequently co-occurring with uveitis.
• The precise causal relationship and underlying mechanisms connecting PsA and uveitis are not well understood.

Purpose of the Study:

• To investigate the causal link between PsA and uveitis.
• To explore the shared genetic and biological mechanisms contributing to their comorbidity.

Main Methods:

• Mendelian randomization (MR) analysis was employed to assess the causal effect of PsA on uveitis risk.
• Gene colocalization and differential gene expression analyses were performed to identify shared genetic factors.
• A nomogram was constructed using key identified genes for predictive assessment.

Main Results:

• MR analysis indicated a significant association between PsA and an increased risk of uveitis (OR = 1.90).
• Four key genes (BAK1, FKBPL, HLA-DQB1, ZKSCAN4) were identified as potentially involved in the shared pathogenesis.
• Functional enrichment analysis highlighted the role of HLA-DQB1 and specific immune cells (eosinophils, neutrophils) in uveitis development.

Conclusions:

• This study provides evidence for a causal relationship between PsA and uveitis.
• Identified genes and immune cell associations offer insights into the shared mechanisms and potential therapeutic targets for PsA-uveitis comorbidity.