Exploring Epidemiology, Gene-Environment Interplay, and Reference Values for Asthma and Associated Phenotypes in a Prospective Child Cohort Study

Background and Significance: Asthma and allergy are worldwide public health problems, which are caused by the complex interplay between genetic factors and environmental exposures. Genome-wide association study (GWAS) represents a powerful method for discovering a new class of novel genes underlying common complex traits. Racial differences in the genetics of asthma and allergy are important areas of research. A GWAS of asthma and allergy in the Chinese population is imperative. New evidence shows high prevalence of vitamin D deficiency in several countries and some studies suggest a possible link between vitamin D status and allergic phenotypes, necessitating further studies. Exposure of children to environmental tobacco smoke (ETS) is a major public health problem, with good evidence showing the adverse impacts of ETS on health, although the mechanism is not fully elucidated. It is now apparent that toll-like receptors (TLRs) of the innate immunity system can also be activated by non-microbial signals, resulting in sterile inflammation that ensures either resolves the initial insult or leads to disease. Notably, new evidence has recently emerged regarding the potential links between the innate immunity and either vitamin D or tobacco smoke, letting us to hypothesize that innate immunity genes may modify associations between environmental exposures and allergic diseases. Few studies report reference values of asthma-associate quantitative traits (e.g., lung function, FeNO, and serum total IgE levels) for Asian populations. Pilot Studies: The opportunity to address these issues stems from the Prediction of Allergies in Taiwanese CHildren (PATCH) Child Cohort, a population-based cohort of more than 1300 subjects with well-documented clinical and laboratory data and blood samples. Our pilot study demonstrated a substantial burden of asthma and allergy in Taiwanese children, as nearly half (48%) of the children surveyed are currently symptomatic for at least one allergic disease and 57.3% having allergic sensitization (J Asthma 2011). Our study demonstrated that FeNO discriminates children with and without allergic sensitization in a population setting (Clin Exp Allergy 2011) and establishes reference values of FeNO for Asian children (Eur Respir J 2012). Our pilot studies established the reference values of serum total IgE levels (PLoS One 2013) and lung function parameters (manuscript in submission) for Asian children. Our pilot study revealed that vitamin D deficiency/insufficiency is remarkably common in Taiwanese children (deficiency, 51% and insufficiency, 90.3%, respectively). Aims and Study Design: Aim 1: Conduct a prospective, longitudinal, population-based cohort study of asthma and associated phenotypes in children. Aim 2: Globally explore genetic markers of asthma and associated phenotypes through a multistage GWAS approach. Aim 3: Investigate the prevalences of vitamin D deficiency and exposure to ETS in children and their impacts on asthma, allergy, lung function, and airway inflammation. Aim 4: Study gene-environment interactions between environmental exposures and innate immunity genes acting on asthma and associated phenotypes in children. Aim 5: Establish updated clinical reference values of quantitative traits related to asthma and allergy (e.g., FeNO, serum total IgE, and lung function). Expected Contributions: This project will provide a better understanding of the epidemiology of asthma and allergic diseases in children, identify genes (and genetic markers) and gene-environment interactions in asthma and allergy, and establish reference values of FeNO, serum total IgE levels and lung function.

Project ID:PC10308-1803
External Project ID:MOST103-2314-B182-030