The Sixteenth Conference of the International Society for Environmental Epidemiology (ISEE): Abstracts
UCLA School of Public Health, Los Angeles, CA
This research was funded in part by the NIEHS-funded UCLA Center for Gene-Environment Studies in Parkinson's Disease and the NIEHS/NINDS Grant 1RO1ES10544.
For human studies of gene-environment interactions in Parkinsons Disease (PD) -including population-based epidemiologic studies - common challenges are to achieve an adequate and prudent selection of candidate genes, an appropriate and detailed characterization of disease phenotypes, a valid and accurate assessment of environmental exposures, and a sufficient sample size for necessary subgroup analyses. I will briefly present our approach to some of these challenges that we employed in 1) a case-control study conducted in Central California; 2) our NIEHS-funded Center for PD, Environment and Genes; and 3) a recent data pooling effort across epidemiologic studies. First, I will briefly show some results from a novel exposure assessment approach of pesticide use that included geographic information system based modeling and serum biomarker analyses. Concerning sample size issues, I believe that they can only be overcome in the long run by data pooling that requires extensive collaboration and trusts among a number of investigators. I will discuss some of the challenges encountered and lessons learned from the first pooled analysis of smoking and PD conducted in collaboration with 9 individual investigators assembling more than 3000 PD cases and 6000 controls. These data allowed us to address issues of relative importance of smoking intensity, duration, and age at starting or stopping smoking for PD. Finally, I will present a novel approach using a high throughput genetic screen to select and test genes that interact with suppressor or enhancers of candidate genes for gene-environment interactions in PD in the fruit fly (Drosophila) model and opportunities to translate these findings to human studies. Studies of lower organisms present unique opportunities for direct manipulation of exposures and genes. Flies' relatively short life span, their extensive use in genetic studies in past decades, and some dopamine dependent behavioral phenotypes uniquely positions them to inform and be informed by epidemiologic studies targeting gene–environment interactions in Parkinsons disease. For example, we expect to identify new modifier genes that can contribute to critical biological functions in neurons when encountering environmental toxins and will use reporter gene assays to identify functional variants in genes central to dopamine metabolism and the potential interaction of enhancer/suppressor genes with these candidate genes.