Fine-mapping Association Analysis of Total IgE on Chr. 20p12 in Costa Ricans

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DESCRIPTION (provided by applicant): Although asthma is a significant public health problem among Hispanics in the United States and in Latin America, little is known about the contribution of genetic factors to the pathogenesis of asthma in this ethnic group. We have previously identified significant evidence of linkage to total serum IgE on chromosome 20p12 among males in a genetically isolated Hispanic population in Costa Rica. This proposal seeks to identify genetic determinants of total serum IgE - a critical intermediate phenotype of asthma- on chromosome 20p12. We will first conduct a fine-mapping association analysis of total serum IgE on chromosome 20p12 in Costa Rican boys with asthma and their parents. We will then attempt to replicate positive findings among families of white (non-Hispanic) boys in the Childhood Asthma Management Program (CAMP). After identification of a susceptibility gene(s) for total IgE in males, we will assess the generalizability of our findings by performing association studies of newly identified candidate genes among families of girls with asthma in both Costa Rica and CAMP. Finally, we will assess the expression of these candidate genes on CD4+ T lymphocytes and examine whether selected variants affect gene expression signatures for total serum IgE among children with asthma in CAMP. This proposal offers a unique opportunity to identify an asthma-susceptibility gene(s) in general and among Hispanics in particular. STATEMENT ON PUBLIC HEALTH RELEVANCE Little is known about the genetics of asthma in Hispanics, despite the disproportionate burden of asthma in certain Hispanic subgroups in both the U.S. and in Latin America. This proposal will utilize state-of-the-art genetic and genomic approaches to help to understand a component of the genetic regulation of total serum IgE, a critical intermediate of asthma, in general and among Hispanics in particular. (End of Abstract)