Background: Viral respiratory infections can cause acute wheezing illnesses in children and exacerbations of asthma. Objective: We sought to identify variation in genes with known antiviral and pro-inflammatory functions to identify specific associations with more severe viral respiratory illnesses and the risk of virus-induced exacerbations during the peak fall season. Methods: The associations between genetic variation at 326 SNPs in 63 candidate genes and 10 phenotypes related to viral respiratory infection and asthma control were examined in 226 children enrolled in the RhinoGen study. Replication of asthma control phenotypes was performed in 2128 children in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Significant associations in RhinoGen were further validated using virus-induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled in the Childhood Origins of Asthma (COAST) birth cohort study. Results: A significant excess of P values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment of small P values. Six of those genes (STAT4, JAK2, MX1, VDR, DDX58, and EIF2AK2) also showed significant associations with asthma exacerbations in the COPSAC study or with asthma or virus-induced wheezing phenotypes in the COAST study. Conclusions: We identified genetic factors contributing to individual differences in childhood viral respiratory illnesses and virus-induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus-induced exacerbations of asthma.
Bibliographical noteFunding Information:
RhinoGen was supported by NIH grant U19 AI070503 and UL1TR000427 (Clinical and Translational Science Award); the COAST study is supported by NIH grant P01 HL070831; and DAL was supported by NIH grants F32 HL095268 and T32 HL007605. Genotyping services were provided through the RS&G Service at Johns Hopkins University under U.S. Federal Government contract number HHSN268201100037C from the National Heart, Lung, and Blood Institute. COPSAC is supported by private and public research funds all listed on www.copsac. com. The Lundbeck Foundation; The Danish Ministry of Health; Danish Council for Strategic Research; The Danish Council for Independent Research and The Capital Region Research Foundation have provided core support for COPSAC.
© 2016 John Wiley & Sons Ltd.
- Allergic sensitization
- Cold symptoms
- Genetic association
- Human rhinovirus
- Viral respiratory illness