Association of Asthma Risk Alleles With Acute Respiratory Tract Infections and Wheezing Illnesses in Young Children

Abstract

Background Genome-wide association studies have identified several risk alleles for early childhood asthma, particularly in the 17q21 locus and in the cadherin-related family member 3 (CDHR3) gene. Contribution of these alleles to the risk of acute respiratory tract infections (ARI) in the early childhood is unclear. Methods We analyzed data from the STEPS birth-cohort study of unselected children and the VINKU and VINKU2 studies on children with severe wheezing illness. Genome-wide genotyping was performed on 1011 children. We analyzed the association between 11 pre-selected asthma risk alleles and the risk of ARIs and wheezing illnesses of various viral etiologies. Results The asthma risk alleles in CDHR3, GSDMA, and GSDMB were associated with an increased rate of ARIs (for CDHR3, incidence rate ratio [IRR], 1.06; 95% CI, 1.01-1.12; P=0.02), and risk allele in CDHR3 gene with rhinovirus infections (IRR, 1.10; 95% CI, 1.01-1.20, P=0.03). Asthma risk alleles in GSDMA, GSDMB, IKZF3, ZPBP2, and ORMDL3 genes were associated with wheezing illnesses in early childhood, especially rhinovirus-positive wheezing illnesses. Conclusions Asthma risk alleles were associated with an increased rate of ARIs and an increased risk of viral wheezing illnesses. Non-wheezing and wheezing ARIs and asthma may have shared genetic risk factors.

Genetic susceptibility to acute viral bronchiolitis

“…Genetic variants in genes including TLR4, VDR, and CCR5 have been suggested to be associated with both RSV bronchiolitis and the risk of asthma 12,31 . Additionally, genetic variants in genomic region 17q21 and CDHR3 showed suggestive associations with non-RSV LRI phenotypes and later asthma 20,21,32 .…”