Multi-omics analysis links NFKB1 activation to poor immunosuppressive therapy response in acquired aplastic anemia

Acquired aplastic anemia (AA) is a bone marrow failure syndrome whose pathogenesis remains incompletely understood. This study aimed to explore the genetic determinants underlying AA and identify potential therapeutic targets. We integrated summary data – based Mendelian randomization (SMR) and colocalization analysis to identify genes causally linked to AA. Key candidates were validated using single-cell RNA sequencing to assess their expression and pseudotime dynamics. We explored B-cell – mediated cell communication related to immunosuppressive therapy response. Serum expression of candidate genes was validated and correlated with clinical outcomes. SMR analysis identified 28 genes significantly associated with AA, among which NFKB1 emerged as a central regulatory factor. scRNA-seq data confirmed NFKB1's differential expression in B cells and its dynamic regulation during disease progression. Discussion and conclusion: This study is the first to comprehensively characterize the role of NFKB1 in the pathogenesis of AA through integrated multi-omics analysis and providing novel insights for the development of targeted interventions.