Novel therapeutic targets uncovered by genome-wide integrative analysis in bronchopulmonary dysplasia.

Abstract

Background: Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory disease in extremely premature infants. This study aims to identify gene expression dysregulation and explore various molecular pathways implicated in BPD.

Methods: This study integrated BPD genome-wide association study (GWAS), single-cell transcriptomics (scRNA-seq), and Mendelian randomization (MR) analysis to investigate the causal relationship between gene expression and BPD.

Results: Cell annotation and ligand-receptor analysis highlighted myofibroblasts as the most interactive cell type. Key genes, including CDH4, ENC1, and PAM, were identified as protective factors against BPD, while GRB10 was associated with increased disease risk. Immune metabolism-related pathways showed elevated activity of PAM, GRB10, and ENC1 in epithelial-mesenchymal transition. The Drug-Gene Interaction Database (DGIdb) predicted three drugs-LM10, navoximod, and ziprasidone-that potentially interact with these key genes.

Conclusion: This integrative genome-wide analysis provides valuable insights into the genetic mechanisms underlying BPD. The findings facilitate the identification of novel therapeutic targets and pave the way for personalized treatment strategies for affected neonates.