This project includes several studies designed to examine genetic influences and gene-environment interaction with respect to childhood respiratory illness in several different populations throughout the world with different prevalences of asthma (Southern California, Mexico City, and Wuhan, China). In the spring of 1998, we began collection of buccal cells using intramural funds, as a source of DNA for genetic analysis, among children enrolled in a cohort study of health effects of air pollution in Southern California (USC Children's Health Study). We are also involved in analysis of data from the children's health study on family history. We have initiated a study of childhood asthma among inner city residents of Mexico City. We have enrolled 160 asthmatic children and plan to expand the study to an eventual enrollment of 600 trios. Exposure to ozone in this area is the highest in North America. The third study is a cohort study of middle school students in Wuhan China. During the 1998-99 school year, we enrolled 5051 seventh grade students in the first year of a follow-up study of risk factors for respiratory health outcomes. We also collected buccal cells as a source of genetic material on these children. We have begun analysis of the year one data to examine risk factors for childhood respiratory symptoms. Genetic analysis will be done with respect to candidate genes using a case-cohort design and gene-environment interactions will be examined. Wuhan China is a low asthma incidence area (estimate of 1-2.5% prevalence). Mexico City is has intermediate rates (about 6%) whereas the Southern California population has the high rates seen in recent US studies (about 12%). Both the Wuhan and Mexico City populations are exposed to high levels of particles other ambient air pollutants as well as antigens such as cockroach, believed to be involved in asthma etiology. Exposure to environmental tobacco smoke is particularly high for the Wuhan middle school students - over 75% live in homes with a father who smokes. Exposure to coal burning and farm animals are also common. The study of populations with high and low incidence of asthma can help identify which proposed risk factors for asthma are etiologically related to the disease. Dr. London has developed a program to investigate childhood asthma in three areas with a spectrum of asthma prevalence -- Southern California (high), Mexico City (intermediate) and Wuhan, China (low). The collection of buccal cells on the USC Children's Health Study with intramural funds was so successful that the USC investigators subsequently received extramural RO1 funding to complete the work under the NIEHS/EPA Children Centers. We are now coordinating with the extramural investigators. Funding was received for an NIEHS intercenter collaborative award to examine a number of candidate genes in these samples. For the Mexico City study, enrollment is successfully underway with 160 complete trios and we plan to extend the sample size to 600. Genetic analyses are underway on samples in hand. From the Wuhan study, we have in hand buccal cell samples on 4800 children who have also completed respiratory health questionnaires. We have begun the analysis of questionnaire outcomes and completed extraction of DNA on cases and controls identified from the cohort.