In the United States, asthma prevalence is highest in Puerto Ricans (26%) and lowest in Mexicans (10%). This is paradoxical since both groups are considered """"""""Hispanic"""""""" or """"""""Latino"""""""". Although there are many potential explanations for this observation, including environmental and socioeconomic factors, one potential explanation is that the genetic predisposition to asthma differs among subgroups within the Latino population. Latinos are admixed and share varying proportions of African, Native American and European ancestry. The mixed ancestry of Latinos provides unique opportunities in epidemiological and genetic studies and may be useful in untangling complex gene-gene and gene-environment interactions in disease susceptibility. This proposal will take advantage of clinical data and genomic DNA on 2,100 Puerto Rican and 1,500 Mexican asthma cases and controls collected as part of two large studies of asthma in Latinos (GALA 1 and GALA 2). The goal of this proposal is to perform genome-wide association analyses to identify genetic factors associated with asthma and related phenotypes in Puerto Ricans and Mexicans. In addition, potential interactions between these genetic factors and other genes and environmental variables will be investigated. Specifically, we will: 1) genotype Puerto Rican and Mexican asthma cases and controls using the Affymetrix state-of-art 500K GeneChip arrays, 2) perform genome-wide association analysis on 500K GeneChip data to identify SNPs associated with asthma, asthma severity and bronchodilator response. The analysis will include clinical and demographic characteristics, environmental factors and individual admixture estimates to correct for potential confounders. In addition, admixture mapping analysis will be performed to complement the genome-wide association analysis. Admixture mapping may identify novel regions that harbor racial/ethnic specific alleles for asthma and related phenotypes; and 3) fine map SNPs significantly associated with asthma and related phenotypes in genome-wide analyses (initial-hit SNPs). To our knowledge this is the first proposal to perform a genome-wide association analysis for asthma and related phenotypes in Latinos. Due to the size and scope of this project, the results of this study should substantially increase our understanding of the etiology of asthma and drug response. By gaining a better understanding of asthma risk factors in diverse populations, this proposal is consistent with the goals established by Healthy People 2010, which are to eliminate health disparities among different segments of the population. ? ? ?
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