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

• Published in: The Journal of infectious diseases 2023-10, Vol.228 (8), p.990-998
• Main Authors: Forsström, Ville, Toivonen, Laura, Homil, Kiara, Waris, Matti, Pedersen, Casper-Emil T, Bønnelykke, Klaus, Jartti, Tuomas, Peltola, Ville
• Format: Article
• Language: English
• Subjects: Alleles; Asthma; Children; Chromosome 17; Clinical trials; Genome-wide association studies; Genomes; Genotyping; Infections; Major; Respiratory tract infection; Rhinovirus; Risk factors; Wheezing
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiad075

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 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 preselected 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% confidence interval [CI], 1.01–1.12; P = .02), and risk allele in CDHR3 gene with rhinovirus infections (IRR, 1.10; 95% CI, 1.01–1.20, P = .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. Nonwheezing and wheezing ARIs and asthma may have shared genetic risk factors. Clinical Trials Registration. NCT00494624 and NCT00731575. Previously identified asthma risk alleles were associated with an increased rate of acute respiratory infections in early childhood. Risk allele CDHR3, coding for rhinovirus species C receptor, was associated with an increased rate of rhinovirus infections.