ABSTRACT 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.
Yue et al. (Thu,) studied this question.