Association of Asthma Risk Alleles With Acute Respiratory Tract Infections and Wheezing Illnesses in Young Children. 2023

Ville Forsström, and Laura Toivonen, and Kiara Homil, and Matti Waris, and Casper-Emil T Pedersen, and Klaus Bønnelykke, and Tuomas Jartti, and Ville Peltola
Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.

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. 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. 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. 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.

UI MeSH Term Description Entries
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D012135 Respiratory Sounds Noises, normal and abnormal, heard on auscultation over any part of the RESPIRATORY TRACT. Breathing Sounds,Crackles,Lung Sounds,Pleural Rub,Rales,Rhonchi,Stridor,Wheezing,Breathing Sound,Crackle,Lung Sound,Pleural Rubs,Rale,Respiratory Sound,Rhonchus,Rub, Pleural,Sound, Breathing,Sound, Lung,Sound, Respiratory,Sounds, Breathing,Sounds, Lung,Stridors,Wheezings
D012141 Respiratory Tract Infections Invasion of the host RESPIRATORY SYSTEM by microorganisms, usually leading to pathological processes or diseases. Respiratory System Infections,Upper Respiratory Tract Infection,Upper Respiratory Tract Infections,Infections, Respiratory,Infections, Respiratory Tract,Infections, Upper Respiratory,Infections, Upper Respiratory Tract,Respiratory Infections,Upper Respiratory Infections,Infection, Respiratory System,Infection, Respiratory Tract,Respiratory Infection, Upper,Respiratory System Infection,Respiratory Tract Infection
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D004527 Egg Proteins Proteins which are found in eggs (OVA) from any species. Egg Protein,Egg Shell Protein,Egg Shell Proteins,Egg White Protein,Egg White Proteins,Egg Yolk Protein,Egg Yolk Proteins,Ovum Protein,Ovum Proteins,Yolk Protein,Yolk Proteins,Protein, Egg,Protein, Egg Shell,Protein, Egg White,Protein, Egg Yolk,Protein, Ovum,Protein, Yolk,Proteins, Egg,Proteins, Egg Shell,Proteins, Egg White,Proteins, Egg Yolk,Proteins, Ovum,Proteins, Yolk,Shell Protein, Egg,Shell Proteins, Egg,White Protein, Egg,White Proteins, Egg,Yolk Protein, Egg,Yolk Proteins, Egg
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000070585 Cadherin Related Proteins Membrane proteins that contain at least two typical consecutive CADHERIN motifs but typically more than cadherin or protocadherin proteins. Their overall domain organization also differs from those of cadherins and protocadherins, and contains different and unique cytoplasmic domains. CDHR Proteins,Cadherin-Related Proteins,Proteins, CDHR,Proteins, Cadherin Related,Proteins, Cadherin-Related,Related Proteins, Cadherin
D000483 Alleles Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product. Allelomorphs,Allele,Allelomorph
D001249 Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL). Asthma, Bronchial,Bronchial Asthma,Asthmas

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