title: Prenatal and postnatal genetic influence on lung function development.
abstract: BACKGROUND
  It is unknown to what extent adult lung function genes affect lung function development from birth to childhood.
  
  
  OBJECTIVE
  Our aim was to study the association of candidate genetic variants with neonatal lung function and lung function development until age 7 years.
  
  
  METHODS
  Lung function measurement by means of spirometry with the raised-volume thoracoabdominal compression technique and bronchial responsiveness to methacholine challenge were assessed in 411 high-risk newborns from the Copenhagen Prospective Study on Asthma in Childhood 2000 (COPSAC2000) cohort. Measures were repeated at age 7 years. Genetic risk scores were calculated based on reported single nucleotide polymorphisms for adult lung function (FEV1/forced expiratory vital capacity [FVC] ratio and FEV1) as the number of risk alleles weighted on known effect size. These genetic risk scores were analyzed against lung function measures as z scores at birth (forced expiratory volume in 0.5 seconds [FEV0.5], forced expiratory flow at 50% of functional vital capacity [FEF50], and provocative dose of methacholine causing a 15% decrease in lung function [PD15]) and at age 7 years (FEV1, FEF50, and provocative dose of methacholine causing a 20% decrease in lung function [PD20]) and with development from birth to age 7 years (FEV0.5/1, FEF50, and PD15/20).
  
  
  RESULTS
  The genetic risk scores were not associated with lung function measures at age 1 month, but the FEV1/FVC genetic risk score was associated with reduced FEF50 values at age 7 years (P = .01) and similarly with reduced growth in FEF50 from birth to age 7 years (P = .02). This score was also associated with increased bronchial responsiveness (reduced PD20) at age 7 years (P = .02) and change in responsiveness from birth to age 7 years (P = .05).
  
  
  CONCLUSIONS
  Lung function genetic variants identified in adults were not associated with neonatal lung function or bronchial responsiveness but with the development of these lung function measures during early childhood, suggesting a window of opportunity for interventions targeting these genetic mechanisms.
authors.affiliation: COPSAC, the Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health Sciences, University of Copenhagen, and the Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Copenhagen, Denmark. Electronic address: eskil.kreiner@dbac.dk.
authors.forename: Eskil
authors.initials: E
authors.lastname: Kreiner-Møller
authors.affiliation: COPSAC, the Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health Sciences, University of Copenhagen, and the Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Copenhagen, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Bisgaard
authors.affiliation: COPSAC, the Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health Sciences, University of Copenhagen, and the Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Bønnelykke
mesh_terms: D000328:Adult; D000367:Age Factors; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000254:growth & development* / Q000503:physiopathology*; D008176:Lung Volume Measurements / Q000379:methods; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000503:physiopathology; D011446:Prospective Studies; D013147:Spirometry / Q000379:methods
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride
keywords: Child; asthma; genetics; respiratory function tests