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

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 8years. 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 50.2mL 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.