The EVE Asthma Genetics Consortium: Building Upon GWAS

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DESCRIPTION (provided by applicant): EVE is a consortium comprised of all U.S. investigators who have conducted genome-wide association studies (GWAS) of asthma and whose main objective is to combine results of individual studies to increase the overall power to identify asthma-susceptibility loci. The consortium includes investigators at 10 U.S. institutions with GWAS results for >30,000 individuals representing European American, African American, U.S. Hispanic, and Mexican populations. As part of the initial goals of EVE, investigators aim to develop a common set of >1 million genotyped and imputed SNPs to be tested for association with asthma in this primary sample followed by association statistics to be combined in a grand meta-analysis for asthma gene discovery. In this GO application, we propose four specific aims: 1) to replicate the most significant meta-analysis results in >15,000 asthma cases and controls of European American, African American, and U.S. Hispanic ethnicities; 2) to resequence 5-10 genes associated with asthma in European Americans but not in African Americans or Hispanic cases and controls (>1,500 individuals) to identify rare and common variants that are not well-tagged by SNPs on the genotyping platforms; 3) to conduct additional meta-analyses in the primary sample for asthma associated phenotypes (e.g., measures of lung function, total serum IgE), and to examine interactions with sex, tobacco smoke exposure in infancy, and between genes; and 4) to develop methods that combine data from different types of study samples (case-control, trios, cohorts) for the meta-analyses described in Aim 3, and integrate network and pathway analyses into our approaches for gene discovery. Discovery of risk alleles for asthma and its associated phenotypes could significantly impact public health and health care delivery by allowing for population screening to identify at-risk individuals who could be candidates for early intervention (disease prevention) or for personalized therapeutics based on molecular pathology rather than on symptomology (disease treatment). PUBLIC HEALTH RELEVANCE: EVE is a consortium comprised of all U.S. investigators who have conducted genome-wide association studies (GWAS) of asthma and whose main objective is to combine results of individual studies to increase the overall power to identify asthma-susceptibility loci. The consortium includes investigators at 10 U.S. institutions with GWAS results for >30,000 individuals representing European American, African American, U.S. Hispanic, and Mexican populations. In this application, we propose to replicate the most significant GWAS results in >15,000 asthma cases and controls of European American, African American, and U.S. Hispanic ethnicities, resequence 5-10 genes associated with asthma in European Americans but not in African Americans or Hispanic cases and controls, to study additional asthma-associated phenotypes and examine interactions, and develop methods to facilitate gene discovery. Discovery of risk alleles for asthma and its associated phenotypes could significantly impact public health and health care delivery.