Adipose tissue transcriptomics associate with 'obesity-related asthma'

<bold>Rationale:</bold> Obesity is associated with higher risk of asthma. Mechanisms are not fully understood, and to date no pediatric studies have analyzed gene expression in adipose tissue (AT). <bold>Methods:</bold> We obtained subcutaneous AT in a prospective cohort of children with and without asthma, performed RNA-sequencing, and completed a transcriptome-wide analysis of asthma, overweight/obesity ("ov/ob", BMI ≥85 pct), and their interaction. Models were adjusted for age, sex, race, study phase, and RNAseq batch. Differentially expressed genes (DEGs) were those with FDR-p<0.05 and |L2FC|≥1.5. <bold>Results:</bold> We analyzed AT from 97 children: 54 with asthma (61% male, 57% ov/ob, mean age 14.0±2.6 yrs) and 43 controls (58% male, 47% ov/ob, 13.9±2.7 yrs). At p < 0.01, we identified 1910 genes associated with asthma, 806 for ov/ob, and 613 for their interaction. At FDR-p<0.05, this included 71 asthma DEGs (Fig. 1A), 60 ov/ob DEGs, and 23 interaction DEGs. Fig. 1B shows the full (main+interaction) effects for 46 DEGs in children with obesity-related asthma, including biologically plausible genes like <italic>SFRP5, DUOX2, CLDN1, CLDN19, NOS1, PCDH8,</italic> and <italic>PTGDR2</italic>. Enriched upregulated pathways included adipogenesis, interferon responses, and TNFα/NFκB signaling (Fig. 1C). <bold>Conclusions:</bold> In this first study of adipose tissue transcriptomics, we found gene expression profiles associated with pediatric obese asthma. Replication is ongoing, as are analyses of asthma severity measures. <fig><object-id>erj;64/suppl_68/OA3658/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>