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Investigation of novel genes for lung function in children and their interaction with tobacco smoke exposure: a preliminary report
Author(s) -
Panasevich Sviatlana,
Melén Erik,
Hallberg Jenny,
Bergström Anna,
Svartengren Magnus,
Pershagen Göran,
Nyberg Fredrik
Publication year - 2013
Publication title -
acta paediatrica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 115
eISSN - 1651-2227
pISSN - 0803-5253
DOI - 10.1111/apa.12204
Subject(s) - single nucleotide polymorphism , medicine , snp , tobacco smoke , allele , lung function , genome wide association study , minor allele frequency , cohort , genetic association , genotype , genetics , lung , gene , biology , environmental health
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 SNP s in adults, 21 were available in our genome‐wide association study data set, either directly genotyped or as proxy SNP s. We tested for association with lung function ( FEV 1 , FVC , FEV 1 / 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 FEV 1 (p = 0.007) and variant allele C in ADAM19 rs2277027 with 1% unit lower FEV 1 /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 FEV 1 /FVC% in exposed children, but not in unexposed (p for interaction 0.04). Conclusion Our data replicate in children an association for TNS 1 , ADAM 19 , THSD 4 and ADCY 2 gene variants with lung function and suggest that interaction with tobacco smoke exposure may be of importance.