Nocturnal asthma is affected by genetic interactions between RORA and NPSR1

Abstract

Background Neuropeptide S Receptor 1 ( NPSR1) and Retinoid Acid Receptor‐Related Orphan Receptor Alpha (RORA ) interact biologically, are both known candidate genes for asthma, and are involved in controlling circadian rhythm. Thus, we assessed (1) whether interactions between RORA and NPSR1 specifically affect the nocturnal asthma phenotype and (2) how this may differ from other asthma phenotypes. Methods Interaction effects between 24 single‐nucleotide polymorphisms (SNPs) in RORA and 35 SNPs in NPSR1 on asthma and nocturnal asthma symptoms were determined in 1432 subjects (763 asthmatics [192 with nocturnal asthma symptoms]; 669 controls) from the Multicenter Asthma Genetic in Childhood/International Study of Asthma and Allergies in Childhood studies. The results were validated and extended in children from the Manchester Asthma and Allergy Study (N = 723) and the Children Allergy Milieu Stockholm and Epidemiological cohort (N = 1646). Results RORA* NPSR1 interactions seemed to affect both asthma and nocturnal asthma. In stratified analyses, however, interactions mainly affected nocturnal asthma and less so asthma without nocturnal symptoms or asthma severity. Results were replicated in two independent cohorts and seemed to remain constant over time throughout youth. Conclusion RORA* NPSR1 interactions appear to be involved in mechanisms specific for nocturnal asthma. In contrast to previous studies focusing on the role of beta 2 receptor polymorphisms in nocturnal asthma as a feature of asthma control or severity in general, our data suggest that changes in circadian rhythm control are associated with nighttime asthma symptoms.

Machine Learning Prediction of Treatment Response to Inhaled Corticosteroids in Asthma

“…Several other genes included in the models were not connected to the ICS response mechanisms per se, but have been linked to asthma severity, asthma control, airway remodeling, and Th2-mediated responses. ABCA7 gene expression is associated with nocturnal asthma symptoms in individuals with a polymorphism in NPSR1 [ 43 ]. BSG (also called CD147 ) is a potential target for asthma treatment therapy.…”

Pediatric pulmonology 2019 year in review: Asthma

“…Retinoic acid receptor related orphan receptor alpha (RORA) and Neuropeptide S receptor 1 (NPSR1) are potential asthma genes that have recently been shown to regulate circadian rhythm. Using large cohorts from previous asthma studies, Gartner et al 9 found that interactions between RORA and NPSR1 SNPs were strongly associated with nocturnal asthma rather than strictly asthma in general. Limitations include questionnaire‐based definition of nocturnal asthma and the fact that this was a retrospective study.…”