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. We conducted a genome-wide association study to examine the genetic contributions to bronchiolitis susceptibility in the FinnGen project data. We analyzed 1465 infants hospitalized for bronchiolitis who were <2 years of age and 356 404 individuals without a history of acute lower respiratory infections. The genome-wide association study 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 as compared with controls. The 2 associated loci were previously linked to asthma and susceptibility to wheezing illness by causative agents other than respiratory syncytial virus (RSV). The identified loci were associated with overall bronchiolitis, with larger effects in non-RSV than RSV-induced infection. Our results suggest that genetic variants in CDHR3 and GSDMB modulate susceptibility to bronchiolitis, especially when caused by viruses other than RSV. Severe bronchiolitis in infancy may trigger the development of asthma in genetically susceptible individuals, or it could be a marker of genetic predisposition to asthma.