Asthma is caused by the interaction of genetic and environmental factors. In the U.S., asthma prevalence, morbidity and mortality are highest in Puerto Ricans, intermediate in Dominicans and Cubans, and lowest in Mexicans and Central Americans. There are many potential explanations for this observation, including place of birth, acculturation, early life exposures and genetic predisposition. 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 of complex traits and may be useful in untangling complex gene-environment (G x E) interactions in disease susceptibility. We hypothesize that ancestry will modify the association between environmental risk factors and asthma prevalence and severity. We propose to investigate whether individual ancestry, genetic factors, and environmental risk factors interact to influence asthma and asthma-related traits among several Latino ethnic groups. We will collect a well-characterized sample of Latino asthmatics (n = 2000) and clinic-based controls (n = 2000), age 8-21 years, from the Bronx, NY, Chicago, IL, San Francisco, CA, Houston, TX and Puerto Rico. This application has three specific aims. 1) We will test the hypothesis that genetic ancestry interacts with environmental/demographic risk factors to modify asthma risk and asthma-related phenotypes in Latinos of high risk Puerto Rican, intermediate risk Dominican, and low risk Central American and Mexican ethnicities. 2) We will genotype fifty candidate genes that may be involved in G x E interactions relevant to asthma. We will test whether there are ethnic-specific G x E interactions that differentially affect asthma risk, severity and pharmacologic response among Latino ethnic groups. 3) We will determine whether migration and acculturation are associated with asthma and severe asthma. Place of birth and length of stay in the U.S. are indicators of migration and acculturation. We will test the hypotheses that these indicators are associated with asthma and asthma severity. We will also test the hypothesis that place of birth and length of stay in the U.S. interact with ancestry, environmental, clinical and demographic risk factors to modify their associations with asthma and asthma severity among Latinos. The diversity and similarity among Latinos provide a valuable opportunity to study the interactions of race, genetics, culture, and environment. By taking advantage of such diversity, we may gain a much more thorough understanding of asthma, its causes, and its distribution among Latinos and other ethnic groups.