Asthma and chronic obstructive pulmonary disease (COPD) are the most common chronic diseases of the lung. Genetic approaches may elucidate the causes of these diseases and thus offer the promise of providing new avenues for their prevention and treatment. We will perform a genome-wide association study of asthma and its lung function phenotypes (bronchodilator responsiveness and spirometric measures of lung function (post bronchodilator FEVi, and FEV^FVC ratio). Wewill genotype 317,504 HapMap SNPs in 400 nuclear families of children with asthma in the CAMP study. We will identify regions potentially containing genetic determinants of asthma and its lung function phenotypes using the PBAT screening algorithm, and we will formally test those regions using FBAT. Replication: Wewill attempt to replicate the most significant associations between SNPs genotyped in Specific Aim 1 and asthma or its lung function phenotypes: For asthma, by performing an analysis of association between 3,072 SNPs and asthma in the Sepracor/EMGB study of 400 cases of asthma and 400 controls, for lung function phenotypes, by performing an analysis of association between these 3,072 SNPs genotyped for Specific Aim 2b and lung function phenotypes among 400 cases of asthma in Sepracor. Identification of Susceptibility Genes for Asthma and/or COPD: We will genotype 1536 SNPs in potential susceptibility genes for asthma and/or COPD (identified by the genome-wide association study of asthma and its lung function phenotypes in Project 1, by candidate-gene association studies of COPD in Project 2, and by QTL studies of asthma and COPD-related phenotypes in mice in Project 3) in three asthma studies: 694 parent-child trios in the CAMP study (including all white, African-American and Hispanic trios), 400 cases and 400 controls in the Sepracor /EMGB study, and 600 nuclear families of children with asthma in Costa Rica. We will use family-based and case- control association analysis to identify genes associated with asthma and/or COPD. This research project will utilize novel and complementary approaches (genome-wide study of association, candidate-gene association studies, andgenetic studies in mice) to findmajor susceptibility genes for asthma andto identify asubset of genes that influence both asthma and COPD.
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