A Novel piRNA Associates with T2-high Asthma Phenotypes

Background Piwi-interacting RNA (piRNA), the largest non-coding RNA group, regulate transcriptional processes. Whether piRNAs are associated with T2-high asthma is unknown. Objective We sought to investigate the association between piRNAs and T2-high asthma in childhood asthma. Methods We sequenced plasma samples from 462 subjects in the Childhood Asthma Management Program (CAMP) as the discovery cohort and 1,165 subjects in the Genetics of Asthma in Costa Rica Study (GACRS) as a replication cohort. Sequencing reads were filtered first and piRNA reads were annotated and normalized. Linear regression was used for the association analysis of piRNAs and peripheral blood eosinophil count, total serum IgE level and long-term asthma exacerbation in children with asthma. Mediation analysis was performed to investigate the effect direction. We then ascertained if the circulating piRNAs were present in asthmatic airway epithelial cells in a GEO public dataset. Results Fifteen piRNAs were significantly associated with eosinophil count in CAMP (p≤0.05), and three were successfully replicated in GACRS. Eleven piRNAs were associated with total IgE in CAMP, and one of these was replicated in GACRS. All 22 significant piRNAs were identified in epithelial cells in vitro, and six of these were differentially expressed between subjects with asthma and healthy controls. Fourteen piRNAs were associated with the long-term asthma exacerbation and effect of piRNAs on the long-term asthma exacerbation are mediated through eosinophils count and serum IgE level. Conclusion piRNAs are associated with peripheral blood eosinophils and total serum IgE in childhood asthma and may play important roles in T2-high asthma.