For a study, researchers sought to discover differentially expressed genes and pathways linked to obesity-related asthma by using a transcriptome study of nasal airway epithelium. Using RNA sequencing data from a cohort of 235 people aged 9–20 years (EVA-PR) and an independent cohort of 66 children aged 6–16 years in Pittsburgh, investigators compared the whole transcriptome in the nasal airway epithelium of youth with overweight or obesity and asthma to that of youth with normal weight and asthma (VDKA). In each cohort, differential expression analysis was done independently, adjusted for age, sex, sequencing plate number, sample sorting process, and the first 5 main components. In a transcriptome-wide meta-analysis, the results from the 2 cohorts were pooled. On the top genes, gene enrichment and network analysis were done. At an FDR-adjusted P<.05, 29 genes were associated with obesity-related asthma in the meta-analysis, including pro-inflammatory genes that are differentially expressed in obese persons’ fatty tissue (e.g., CXCL11, CXCL10, and CXCL9) and several novel genes. In overweight/obese kids with asthma, functional enrichment studies revealed that pathways for interferon signaling and innate and adaptive immunological responses were down-regulated. In contrast, pathways linked to ciliary structure or function were up-regulated. The upstream regulatory study anticipated that the IRF7 pathway would be significantly inhibited. GBP5 and SOCS1 were identified as “hub” genes in network analysis. The transcriptome-wide investigation of the nasal airway epithelium discovered biologically plausible genes and pathways associated with obesity-related asthma in children and adolescents.