Violence‐Related Distress, Nasal Epithelial Gene Expression, and T17‐High Asthma in Youth

BACKGROUND: Little is known about the mechanisms underlying the link between violence-related distress and asthma, particularly for asthma endotypes. METHODS: Cross-sectional analysis of violence-related distress in the previous 6 months (assessed using the Checklist of Children's Distress Symptoms [CCDS] scale) and nasal epithelial gene expression in 3 studies of youth with asthma aged 8-20 years: Stress and Treatment Response in Puerto Rican and African American Children with Asthma (STAR, n = 128), Epigenetic Variation and Childhood Asthma in Puerto Ricans (EVA-PR, n = 228), and Vitamin D Kids Asthma (VDKA, n = 47). We then tested for the association between expression of CCDS-related genes and nasal epithelial transcriptomic profiles corresponding to T2-high and T17-high asthma endotypes. RESULTS: In a meta-analysis of the CCDS score in the three cohorts, we identified 12 differentially expressed genes (DEGs) with false discovery rate-adjusted p value (FDR-P) < 0.05 and the same direction of association as in the discovery cohort (EVA-PR) in at least one replication cohort. Of these 12 DEGs, 9 (S100A7A, CCL2, CCL8, CXCL9-11, COL15A1, CD300E, and LILRB1) were upregulated and significantly associated with T17-high asthma in a meta-analysis of the three cohorts. Two genes belong to the CC Motif Chemokine Ligand family (CCL2, CCL8) and 3 belong to the CXC Motif Chemokine Ligand family (CXCL9, CXCL10, and CXCL11). CONCLUSION: Nine novel genes were associated with violence-related distress and T17-high asthma in three cohorts of predominantly minoritized youth with asthma. Our findings may help uncover biologic processes underlying the violence-asthma link and could represent novel therapeutic targets for T17-high asthma.