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MECHANISTIC INDICATORS OF CHILDHOOD ASTHMA (MICA): A SYSTEMS BIOLOGY APPROACH FOR THE INTEGRATION OF MULTIFACTORIAL EXPOSURE AND ENVIRONMENTAL HEALTH DATA
Citation:
HUDGENS, E. E., D. REIF, A. H. WILLIAMS, M. M. JOHNSON, S. W. RHONEY, J. P. INMON, R. W. WILLIAMS, L. M. NEAS, H. A. OZKAYNAK, B. HEIDENFELDER, E. Cohen-Hubai, S. W. EDWARDS, AND J. GALLAGHER. MECHANISTIC INDICATORS OF CHILDHOOD ASTHMA (MICA): A SYSTEMS BIOLOGY APPROACH FOR THE INTEGRATION OF MULTIFACTORIAL EXPOSURE AND ENVIRONMENTAL HEALTH DATA. Presented at American Association for Aerosol Research (AAAR), San Diego, CA, March 22 - 26, 2010.
Impact/Purpose:
The objectives of MICA study are: 1) the identification of biologically relevant air pollution species and sources through indoor I outdoor home monitoring and vacuum dust analyses 2) application of exposure, effect, clinical, and gene biomarkers to evaluate both overarching and specific studies along the source to health outcome paradigm 3) identification of panels ofbiomarkers from the array of MICA co-variants for future application in large population studies to provide linkages between exposure and health outcome.
Description:
Modem methods in molecular biology and advanced computational tools show promise in elucidating complex interactions that occur between genes and environmental factors in diseases such as asthma. However, appropriately designed studies are critical for these methods to reach their full potential. We provide a framework for the study design by using an exposure to health outcome case-control study to investigate whether genomic data (blood gene expression and single nucleotide polymorphisms) viewed together with a spectrum of exposure, effects and susceptibility markers measured in blood, urine, nail, DNA and RNA, provide a mechanistic explanation for the increased susceptibility of asthmatic children to ambient air pollutants. We studied 205 non-asthmatic and asthmatic children, 9-12 years of age, who participated in a clinicbased study in the Detroit, Michigan metropolitan area. The study combined a traditional epidemiologic design with an integrative clinical approach focused on immunological, cardiovascular and respiratory measurements. The objectives of MICA study are: 1) the identification of biologically relevant air pollution species and sources through indoor I outdoor home monitoring and vacuum dust analyses 2) application of exposure, effect, clinical, and gene biomarkers to evaluate both overarching and specific studies along the source to health outcome paradigm 3) identification of panels ofbiomarkers from the array of MICA co-variants for future application in large population studies to provide linkages between exposure and health outcome. These markers are assessed by addressing their reliability, predictive value, sensitivity, specificity, affordability, applicability 4) application of statistical and methodological approaches to define potential asthma phenotypes and identify underlying mechanisms related to perturbation of gene networks related to environmental exposures and or genetic susceptibility. Initial results from our analyses point to the complex nature ofchildhood health based on risk . factors associated with asthma and childhood obesity. For example, 31% and ofthe asthmatic MICA subjects are either overweight (BMI > 25) or hypertensive (34%) based on age and gender adjusted blood pressure values exceeding Centers for Disease Control 90th percentile values. The study design represents a new paradigm for epidemiologic studies in which traditional health endpoints and biomarkers are coupled with genetics and high content (Omics) data to expand the use of mechanistic models for human risk assessment. This abstract is the text