Integrating Metabolomic and Genomic Approaches to Develop Novel Biomarkers for Diagnosis and Prognosis in Childhood Asthma

Background and Significance: Asthma is a common complex disease imposing a substantial burden on children. It is well known that most asthma has its origins in early childhood. Yet the natural history and progression of childhood asthma is not well described. This is partly due to the few number of prospective population-based cohort studies addressing this issue. Little is known about the longitudinal outcomes of childhood asthma, particularly the rates and predictors of persistence or remission. Thus far, there is a lack of predictive models for the course of childhood asthma, especially during the period of transition from childhood to adulthood. There is an unmet need for appropriate reference values of asthma-associated quantitative traits and other potentially useful biomarkers for Taiwanese children. Asthma is very heterogeneous in onset, response to treatment and outcome, and seems to encompass a broad collection of heterogeneous disease subtypes with different underlying pathophysiological mechanisms. There is a strong need for easily interpreted biomarkers of asthma for clinical practice. Potential candidate biomarkers of interest in this project include but not limited to fraction of exhaled nitric oxide (FeNO), lung function, total and specific immunoglobulin E (IgE), vitamin D, cotinine, periostin, leukotriene E4 (LTE4), sCD14, and adipokines. Systems approaches including genomics, metabolomics and further integrating these attempts provide deeper understanding of complex diseases. Genome-wide association study (GWAS) is a powerful tool 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. Metabolomic profiling, the study of ideally all small molecules (＜1 kDa) generated from metabolic activity in a biological sample, has been shown to be a valuable tool for the discovery of biomarkers and for the elucidation of mechanisms in complex diseases. Integrating genomic and metabolomic information may allow the simultanenous analysis of the genetic and environmental impact on the development and pathogenesis of asthma. Study Subjects: The Prediction of Allergies in Taiwanese CHildren (PATCH) Child Cohort is a population-based cohort of more than 1300 subjects with well-defined clinical and laboratory data and biological specimens. We have recently published several first/corresponding author papers on well-known SCI journals (J Asthma 2011; Clin Exp Allergy 2011; Eur Respir J 2012; PLoS One 2013; J Allergy Clin Immunol 2014; Allergy 2014; PLoS One 2014; J Pediatr 2014; J Allergy Clin Immunol [manuscript in revision]). The PATCH Birth Cohort serves as an independent validation cohort. Aims and Study Design: Aim 1: Evaluate the roles of candidate biomarkers for diagnosis and prognosis of childhood asthma. Aim 2: Systemically explore genomic biomarkers of childhood asthma. Aim 3: Systemically explore metabolomic biomarkers of childhood asthma. Aim 4: Integrative analysis of genome and metabolome of childhood asthma. Aim 5: Develop outcome prediction models of childhood asthma. Aim 6: Establish appropriate reference values of asthma biomarkers. Expected Contributions: This prospective, longitudinal, population-based cohort study of asthma and associated phenotypes in children will systemically develop novel biomarkers for diagnosis and prognosis in childhood asthma through integrated metabolomic and genomic approaches.

Project ID:PC10408-2395
External Project ID:MOST104-2314-B182-046-MY2