TY - JOUR
T1 - Genome-wide association study of polymorphisms predisposing to bronchiolitis
AU - Pasanen, Anu
AU - Karjalainen, Minna K.
AU - Bont, Louis
AU - Piippo-Savolainen, Eija
AU - Ruotsalainen, Marja
AU - Goksör, Emma
AU - Kumawat, Kuldeep
AU - Hodemaekers, Hennie M
AU - Nuolivirta, Kirsi
AU - Jartti, Tuomas
AU - Wennergren, Göran
AU - Hallman, Mikko
AU - Rämet, Mika
AU - Korppi, Matti
PY - 2017/1/31
Y1 - 2017/1/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85011299441&partnerID=8YFLogxK
U2 - 10.1038/srep41653
DO - 10.1038/srep41653
M3 - Article
C2 - 28139761
AN - SCOPUS:85011299441
SN - 2045-2322
VL - 7
JO - Scientific Reports
JF - Scientific Reports
M1 - 41653
ER -