Traffic, asthma and genetics: combining international birth cohort data to examine genetics as a mediator of traffic-related air pollution’s impact on childhood asthma

Elaina A. MacIntyre, Christopher Carlsten, Meaghan MacNutt, Elaine Fuertes, Eric Melén, Carla M. T. Tiesler, Ulrike Gehring, Ursula Krämer, Claudia Klümper, Marjan Kerkhof, Moira Chan-Yeung, Anita L. Kozyrskyj, Dietrich Berdel, Carl Peter Bauer, Olf Herbarth, Mario Bauer, Beate Schaaf, Sibylle Koletzko, Goran Pershagen, Bert Brunekreef, Joachim Heinrich, Michael Brauer

Associations between traffic-related air pollution and incident childhood asthma can be strengthened by analysis of gene-environment interactions, but studies have typically been limited by lack of study power. We combined data from six birth cohorts on: asthma, eczema and allergic rhinitis to 7/8 years, and candidate genes. Individual-level assessment of traffic-related air pollution exposure was estimated using land use regression or dispersion modeling. A total of 11,760 children were included in the Traffic, Asthma and Genetics (TAG) Study; 6.3 % reported physician-diagnosed asthma at school-age, 16.0 % had asthma at anytime during childhood, 14.1 % had allergic rhinitis at school-age, 10.0 % had eczema at school-age and 33.1 % were sensitized to any allergen. For GSTP1 rs1138272, the prevalence of heterozygosity was 16 % (range amongst individual cohorts, 11-17 %) and homozygosity for the minor allele was 1 % (0-2 %). For GSTP1 rs1695, the prevalence of heterozygosity was 45 % (40-48 %) and homozygosity for the minor allele, 12 % (10-12 %). For TNF rs1800629, the prevalence of heterozygosity was 29 % (25-32 %) and homozygosity for the minor allele, 3 % (1-3 %). TAG comprises a rich database, the largest of its kind, for investigating the effect of genotype on the association between air pollution and childhood allergic disease.