Genetic susceptibility to acute viral bronchiolitis

Abstract

Acute viral bronchiolitis is a major cause of infant hospitalizations worldwide. Childhood bronchiolitis is considered a risk factor for asthma, suggesting shared genetic factors and biological pathways. Genetic risk loci may provide new insights into disease pathogenesis. Here, we examined the genetic contributions to bronchiolitis susceptibility by analyzing 1,465 infants hospitalized for bronchiolitis and 356,404 individuals without a history of acute lower respiratory tract infections in the FinnGen project data. Genome-wide analysis identified associations (p<5*10-8) for variants in gasdermin B (GSDMB) and a missense variant in cadherin-related family member 3 (CDHR3). Children with bronchiolitis in infancy were more likely to develop asthma later in life compared to controls. The two associated loci were previously linked to asthma and susceptibility to wheezing illness by other causative agents than RSV. Our analysis discovered associations with overall bronchiolitis, with larger effects in non-RSV than RSV-induced infection. Our results suggest that genetic variants inCDHR3andGSDMBmodulate susceptibility to bronchiolitis, especially when caused by viruses other than RSV, and that severe bronchiolitis in infancy may trigger the development of asthma in genetically susceptible individuals determined by these loci.