Investigation of novel genes for lung function in children and their interaction with tobacco smoke exposure: a preliminary report

Abstract

Aim: To replicate newly reported single nucleotide polymorphism (SNP) associations with adult lung function in a cohort of children and to investigate interactions with tobacco smoke exposure on lung function.

Methods: Of 37 reported SNPs in adults, 21 were available in our genome-wide association study data set, either directly genotyped or as proxy SNPs. We tested for association with lung function (FEV1 , FVC, FEV1 /FVC%) in 8-year-old children and analysed interaction with tobacco smoke exposure both prenatally and/or during infancy, as well as at the age of 8 years.

Results: SNPs in TNS1, ADAM19, THSD4 and ADCY2 showed significant association with lung function in children, although ADCY2 variants not in the expected direction. For example, variant allele A in THSD4 rs12899618 was associated with 50.2 mL higher FEV1 (p = 0.007) and variant allele C in ADAM19 rs2277027 with 1% unit lower FEV1 /FVC% (p = 0.03) per allele. DAAM2 rs2395730 showed interaction with current tobacco smoke exposure, with variant C allele associated with 1.3% unit decrease in FEV1 /FVC% in exposed children, but not in unexposed (p for interaction 0.04).

Conclusion: Our data replicate in children an association for TNS1, ADAM19, THSD4 and ADCY2 gene variants with lung function and suggest that interaction with tobacco smoke exposure may be of importance.