Genome-Wide Association Study of Polymorphisms Predisposing to Bronchiolitis

• DOI: 10.1038/srep41653
• Publication Date: 2017-01-31T11:15:27Z
• Authors: Anu Pasanen; Minna K. Karjalainen; Louis Bont; Eija Piippo-Savol...; Marja Ruotsalainen; Emma Goksör; Kuldeep Kumawat; Hennie Hodemaekers; Kirsi Nuolivirta; Tuomas Jartti; Göran Wennergren; Mikko Hallman; Mika Rämet; Matti Korppi
• Keywords: Male; Genotype; Respiratory Syncytial Virus Infections; Paediatric research; Polymorphism, Single Nucleotide; Article; 03 medical and health sciences; 0302 clinical medicine; Genetics research; Journal Article; Odds Ratio; Humans; Genetic Predisposition to Disease; General; Alleles; Genetic Association Studies; Genetic association study; Biolääketieteet – Biomedicine; Medical genetics; Naisten- ja lastentaudit - Gynaecology and paediatrics; ta3123; Asthma; 3. Good health; Respiratory Syncytial Virus, Human; Bronchiolitis; Female; Genome-Wide Association Study

AbstractBronchiolitis 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.