The long -term goal of this research is to determine the relative contributions of genetic and environmental factors in the etiology of typical PD. This work will extend ongoing investigations of both risk and protective factors for PD in four unique populations: the NAS /NRC World War II Veteran Twins cohort (TWINS), the Agricultural Health Study of Farming and Movement Evaluation (FAME ), the Honolulu Asian Aging Study (HAAS ), and the PD Epidemiology at Kaiser project (PEAK). By taking advantage of both the unique and the common features of each cohort, unresolved questions regarding risk and protective factors for PD will be addressed. In particular, by pooling data and results from the four studies, it will be possible to address important questions on gene-environment interactions that require a larger sample size than is available in a single study. The investigators will take advantage of exciting new work identifying polymorphisms in specific membrane transporters for xenobiotics and new and existing state-of-the-art exposure assessment methods in these four cohorts to investigate important gene-environment interactions in PD. This work will be carefully coordinated with each of the other projects in this application and will extend the questions addressed by those integrated research projects to human populations, thereby directly assessing their relevance to PD. The investigators' work in all four cohorts is dedicated to exploring the relative contributions of genetic and environmental factors to PD and is therefore highly relevant to the CCPDER concept. Observations in these populations have already provided pivotal insights regarding the importance of environmental determinants to the cause of PD and the strong inverse (and thus potentially neuroprotective) associations of cigarette smoking and coffee drinking. In this application, the investigators propose to extend these observations in order to obtain clues to the underlying causes of these inverse associations. In addition, they will investigate the hypothesis that differential susceptibility to xenobiotic exposure affects the risk for PD. The investigators will do this by investigating specific genetic variants in xenobiotic transporters, both alone and in combination with transporter-specific exposures. They plan to explore these questions within individual cohorts, as well as in a combined analysis .
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