Superfund Research Program
Environmental and Genetic Risk Factors for Parkinson's Disease
Project Leader: Harvey Checkoway (University of California-San Diego)
Grant Number: P42ES004696
Funding Period: 1995 - 2009
Project-Specific Links
Final Progress Reports
PublicationsConnect with the Grant Recipients
Final Progress Reports
This project is investigating the roles of environmental factors and genetic susceptibility traits in the causation of Parkinson’s disease (PD). The environmental agents of greatest interest are those that have the potential to damage (or protect) nerve cells that produce the neurotransmitter dopamine as depletion of dopamine is the underlying cause of PD. In addition, Dr. Checkoway’s research group is investigating varying forms of genes that may render persons especially sensitive to the effects of environmental chemicals.
The research team continued to enroll PD cases and controls from the membership of Group Health Cooperative of Puget Sound, Washington. They have collected data for 496 cases and 646 controls who meet study eligibility criteria.
Dr. Checkoway’s group continued to observe a consistent pattern of reduced risk among cigarette smokers, as has been found nearly all PD studies. Unlike some other studies, the research group did not observe a reduced risk related to caffeine consumption. Alcohol use was similarly unrelated to PD risk. Their analysis of genetic variants is ongoing. Specifically they noted an elevated risk associated with a variant of the gene that encodes the haptoglobin protein, which removes circulating blood iron. This effect was strongest in never smokers. The remaining analyses of roughly 3000 genetic markers will be completed soon. Dr. Checkoway has established collaborations with 3 groups of investigators conducting PD studies who have agreed to share data on genetic variants for purposes of independent replication of results.
Dr. Checkoway has also established collaborations with several groups of epidemiologists conducting PD studies that, like this study, are focusing on associations with environmental (e.g., pesticides) and lifestyle exposures (e.g., smoking). The collaborators will ultimately pool data from their separate studies to assess consistency of findings, and to enhance statistical precision of risk estimates.
One notable result derived from the collaborations thus far was a very strong inverse risk relation (“protective effect”) among persons who have a history of cigarette smoking, drink relatively large quantities of coffee, and routinely take non-steroidal anti-inflammatory medications. The researchers are continuing to pursue collaborative investigations of interactions between occupational pesticide exposure and variants of the dopamine transporter gene that they identified previously, with investigators from four other studies in North America and Europe.