Hub genes PRPF19 and PPIB in relation to COPD: A Mendelian Randomization investigation

<bold>Background:</bold> COPD, shaped by genetic and environmental factors, requires a nuanced genetic understanding for effective diagnostics and treatment. Robust genetic analysis is crucial for establishing causal relationships. <bold>Methods:</bold> Employing WGCNA on epigenome and transcriptome data, we identified COPD-associated hub genes. DMGs and DEGs were scrutinized between COPD and control samples, revealing five hub genes—PPIB, HSPA2, PRPF19, FKBP10, and DOHH. Protein-protein interaction networks and regulatory elements (TFs and miRNAs) were predicted. MR assessed the genetic connection between hub genes and COPD. Sensitivity analyses validated MR findings, and hub gene expression was confirmed through qPCR and immunohistochemistry. <bold>Results:</bold> 10,593 DMGs and 646 DEGs were linked to COPD. Integrating these with co-expression network module genes unveiled altered expression of the five hub genes. DOHH, FKBP10, PPIB, and PRPF19 exhibited heightened expression, while HSPA2 expression diminished (Fig. 1). Regulatory networks involving TFs and miRNAs were delineated. MR indicated a potential causal link between PRPF19, PPIB, and COPD. Sensitivity analyses reinforced these findings, and validation results remained consistent (Fig. 2). <bold>Conclusion:</bold> PRPF19 and PPIB emerge as promising therapeutic targets and COPD biomarkers, supported by compelling genetic evidence. <fig><object-id>erj;64/suppl_68/PA4391/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>