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

Ville Forsström, Laura Toivonen, Kiara Homil, Matti Waris, Casper-Emil T Pedersen, Klaus Bønnelykke, Tuomas Jartti, Ville Peltola

6 Citations (Scopus)

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.

Original languageEnglish
JournalThe Journal of infectious diseases
Volume228
Issue number8
Pages (from-to)990-998
Number of pages9
ISSN0022-1899
DOIs
Publication statusPublished - 18 Oct 2023

Keywords

  • Humans
  • Child
  • Child, Preschool
  • Alleles
  • Cohort Studies
  • Respiratory Sounds/genetics
  • Genome-Wide Association Study
  • Asthma/epidemiology
  • Respiratory Tract Infections/complications
  • Egg Proteins/genetics
  • Membrane Proteins/genetics
  • Pore Forming Cytotoxic Proteins/genetics
  • Cadherin Related Proteins

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