title: Genome-Wide Association Study of Polymorphisms Predisposing to Bronchiolitis.
abstract: Bronchiolitis is a major cause of hospitalization among infants. Severe bronchiolitis is associated with later asthma, suggesting a common genetic predisposition. Genetic background of bronchiolitis is not well characterized. To identify polymorphisms associated with bronchiolitis, we conducted a genome-wide association study (GWAS) in which 5,300,000 single nucleotide polymorphisms (SNPs) were tested for association in a Finnish-Swedish population of 217 children hospitalized for bronchiolitis and 778 controls. The most promising SNPs (n = 77) were genotyped in a Dutch replication population of 416 cases and 432 controls. Finally, we used a set of 202 Finnish bronchiolitis cases to further investigate candidate SNPs. We did not detect genome-wide significant associations, but several suggestive association signals (p < 10-5) were observed in the GWAS. In the replication population, three SNPs were nominally associated (p < 0.05). Of them, rs269094 was an expression quantitative trait locus (eQTL) for KCND3, previously shown to be associated with occupational asthma. In the additional set of Finnish cases, the association for another SNP (rs9591920) within a noncoding RNA locus was further strengthened. Our results provide a first genome-wide examination of the genetics underlying bronchiolitis. These preliminary findings require further validation in a larger sample size.
authors.affiliation: PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu, and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Pasanen
authors.affiliation: PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu, and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
authors.forename: Minna K
authors.initials: MK
authors.lastname: Karjalainen
authors.affiliation: Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Bont
authors.affiliation: Kuopio University Hospital, Pediatrics, University of Eastern Finland, Kuopio, Finland.
authors.forename: Eija
authors.initials: E
authors.lastname: Piippo-Savolainen
authors.affiliation: Kuopio University Hospital, Pediatrics, University of Eastern Finland, Kuopio, Finland.
authors.forename: Marja
authors.initials: M
authors.lastname: Ruotsalainen
authors.affiliation: Department of Pediatrics, University of Gothenburg, Queen Silvia Children's Hospital, Gothenburg, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Goksör
authors.affiliation: Department of Immunology, Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Kumawat
authors.affiliation: RIVM, National Institute for Public Health and the Environment, GZB, Center for Health Protection, Bilthoven, The Netherlands.
authors.forename: Hennie
authors.initials: H
authors.lastname: Hodemaekers
authors.affiliation: Department of Pediatrics, Seinäjoki Central Hospital, Seinäjoki, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Nuolivirta
authors.affiliation: Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Tuomas
authors.initials: T
authors.lastname: Jartti
authors.affiliation: Department of Pediatrics, University of Gothenburg, Queen Silvia Children's Hospital, Gothenburg, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Wennergren
authors.affiliation: PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu, and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Hallman
authors.affiliation: PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu, and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.|BioMediTech, University of Tampere, Tampere, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Rämet
authors.affiliation: Center for Child Health Research, Tampere University and Tampere University Hospital, Tampere, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Korppi
mesh_terms: D000483:Alleles; D001249:Asthma / Q000235:genetics / Q000821:virology; D001988:Bronchiolitis / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000502:physiology