Genetic and Environmental Determinants of Respiratory Health

Respiratory symptoms and low levels of lung function are main characteristics of respiratory diseases. However, their mechanisms are still unclear. Respiratory symptom can be caused by different environmental exposures or can be a presentation of different underlying diseases with specific genetic or environmental origins. The aim of this thesis is to assess whether environmental exposures are associated with the levels of lung function and respiratory symptoms, and to examine whether the effects of these exposures are dependent on genetic make-up using one Chinese children and two Dutch adult cohort studies (LifeLines and Vlagtwedde-Vlaardingen cohorts). Living in e-waste exposed areas have adverse effects such as higher prevalence of respiratory symptoms and lower levels of lung function on Chinese preschool children. According to genome-wide interaction analysis (GWIS) and expression quantitative trait loci (eQTLs), several SNPs located on TMPRSS9, TOX3, and ARHGAP18 are associated with both one of the respiratory symptoms in subjects with occupational exposures and gene expression levels. SNPs located on ROCK2, GLS and KCTD10 have been found to be associated with one of the respiratory symptoms on SNP-by-NO2 interaction analysis and eQTLs. This information may contribute to the understanding of pathways underlying the development of respiratory symptoms and to the identification of subjects that are genetically susceptible to environmental exposures.