Association of Asthma Risk Alleles With Acute Respiratory Tract Infections and Wheezing Illnesses in Young Children
Open Access
- 27 March 2023
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journal of Infectious Diseases
- Vol. 228 (8), 990-998
- https://doi.org/10.1093/infdis/jiad075
Abstract
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. 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. 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. 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.Keywords
Funding Information
- University of Turku
- Abo Akademi University
- Turku University Hospital
- Academy of Finland (123571, 140251, 277535, 324926)
- Emil Aaltonen Foundation
- Sigrid Juselius Foundation
- Finnish Medical Foundation
- Paivikki and Sakari Sohlberg Foundation
- Foundation for Pediatric Research
- Allergy Research Foundation
- Paulo Foundation
- Hospital District of Southwest Finland
- Tampere Tuberculosis Foundation
- Juho Vainio Foundation
This publication has 32 references indexed in Scilit:
- Rhinovirus Wheezing Illness and Genetic Risk of Childhood-Onset AsthmaThe New England Journal of Medicine, 2013
- Examination of the relationship between variation at 17q21 and childhood wheeze phenotypesJournal of Allergy and Clinical Immunology, 2013
- Prenatal and Passive Smoke Exposure and Incidence of Asthma and Wheeze: Systematic Review and Meta-analysisPEDIATRICS, 2012
- A Large-Scale, Consortium-Based Genomewide Association Study of AsthmaThe New England Journal of Medicine, 2010
- Allele-Specific Chromatin Remodeling in the ZPBP2/GSDMB/ORMDL3 Locus Associated with the Risk of Asthma and Autoimmune DiseaseAmerican Journal of Human Genetics, 2009
- ORMDL3 Gene Is Associated with Asthma in Three Ethnically Diverse PopulationsAmerican Journal of Respiratory and Critical Care Medicine, 2008
- Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthmaNature, 2007
- Prednisolone reduces recurrent wheezing after a first wheezing episode associated with rhinovirus infection or eczemaJournal of Allergy and Clinical Immunology, 2007
- Evaluation of the Efficacy of Prednisolone in Early Wheezing Induced by Rhinovirus or Respiratory Syncytial VirusThe Pediatric Infectious Disease Journal, 2006
- Prospective study of risk factors for early and persistent wheezing in childhoodEuropean Respiratory Journal, 1995