Prenatal and postnatal genetic influence on lung function development

Eskil Kreiner-Møller; Hans Bisgaard; Klaus Bønnelykke

doi:10.1016/j.jaci.2014.04.003

Prenatal and postnatal genetic influence on lung function development

J Allergy Clin Immunol. 2014 Nov;134(5):1036-42.e15. doi: 10.1016/j.jaci.2014.04.003. Epub 2014 May 21.

Authors

Eskil Kreiner-Møller¹, Hans Bisgaard², Klaus Bønnelykke²

Affiliations

¹ 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.
² 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.

PMID: 24857373
DOI: 10.1016/j.jaci.2014.04.003

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).

Conclusion: 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.

Keywords: Child; asthma; genetics; respiratory function tests.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Age Factors
Bronchoconstrictor Agents / administration & dosage
Case-Control Studies
Child
Child, Preschool
Female
Forced Expiratory Volume / drug effects
Forced Expiratory Volume / genetics*
Humans
Infant
Infant, Newborn
Lung / growth & development*
Lung / physiopathology*
Lung Volume Measurements / methods
Male
Methacholine Chloride / administration & dosage
Polymorphism, Single Nucleotide
Pregnancy
Prenatal Exposure Delayed Effects / genetics*
Prenatal Exposure Delayed Effects / physiopathology
Prospective Studies
Spirometry / methods

Substances

Bronchoconstrictor Agents
Methacholine Chloride