title: Genetic associations with viral respiratory illnesses and asthma control in children.
abstract: 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.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.|Department of Biology, Saint Michael's College, Colchester, VT, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Loisel
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.
authors.forename: G
authors.initials: G
authors.lastname: Du
authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Ledreborg Allé 34, DK-2820, Copenhagen, Denmark.|Steno Diabetes Center, Gentofte, Denmark.
authors.forename: T S
authors.initials: TS
authors.lastname: Ahluwalia
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Tisler
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Evans
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Myers
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Gangnon
authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Ledreborg Allé 34, DK-2820, Copenhagen, Denmark.
authors.forename: E
authors.initials: E
authors.lastname: Kreiner-Møller
authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Ledreborg Allé 34, DK-2820, Copenhagen, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Bønnelykke
authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Ledreborg Allé 34, DK-2820, Copenhagen, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Bisgaard
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Jackson
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Lemanske
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.|Department of Medicine, University of Chicago, Chicago, IL, USA.|Department of Statistics, University of Chicago, Chicago, IL, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Nicolae
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Gern
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.
authors.forename: C
authors.initials: C
authors.lastname: Ober
mesh_terms: D000367:Age Factors; D000483:Alleles; D001249:Asthma / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D063868:Patient Outcome Assessment; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D015203:Reproducibility of Results; D012141:Respiratory Tract Infections / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000821:virology*
keywords: allergic sensitization; asthma; children; cold symptoms; genetic association; human rhinovirus; viral respiratory illness; wheezing