The primary goal of this project is to investigate whether certain environmental exposures and genetic variants, either alone or in combination, affect the risk of developing Parkinson's disease (PD). We will investigate mechanisms that may explain the consistently observed inverse associations of cigarette smoking and caffeine consumption with PD, and the role of residential pesticide exposure on the risk of PD. In addition, existing and newly-identified polymorphisms in the coding and regulatory regions of candidate genes will be investigated, including genes that code for: (1) endogenous enzymes involved in metabolism of tobacco or caffeine, or in the detoxification of putative toxicants for PD, (2) proteins involved in dopamine regulation or metabolism, and (3) proteins that play a role in protein degradation and aggregation in dopaminergic neurons. We propose to expand a recently completed case-control study in a large health maintenance population of more than 500 newly diagnosed PD cases and 500 controls. Because preliminary data show that the strongest associations of genetic variants were observed among PD cases with early age at diagnosis (age less than or equal to 60), we will identify approximately 330 additional such cases along with age- and sex-matched controls. This new sample will be combined with that of the previous study, resulting in approximately 420 young diagnosis cases and 430 older diagnosis (age greater than 60) cases to be compared with 870 age- and gender-matched controls. Detailed information will be collected from all study subjects using in- person and telephone structured interviews including information on cigarette smoking, caffeine intake, and residential exposure to pesticides, along with other putative risk factors. Venous blood samples will be drawn for DNA extraction and genotyping assays for the gene polymorphisms of interest. By examining genetic polymorphisms within a group of carefully chosen candidate genes, in combination with extensive information about common environmental exposures, we hope to advance knowledge regarding both genetic and modifiable environmental risk factors for Parkinson's disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS031964-07
Application #
6619382
Study Section
Special Emphasis Panel (ZRG1-EDC-3 (01))
Program Officer
Oliver, Eugene J
Project Start
1994-06-01
Project End
2005-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
7
Fiscal Year
2003
Total Cost
$764,225
Indirect Cost
Name
Stanford University
Department
Miscellaneous
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Kwee, Lydia Coulter; Liu, Yutao; Haynes, Carol et al. (2012) A high-density genome-wide association screen of sporadic ALS in US veterans. PLoS One 7:e32768
McGuire, V; Van Den Eeden, S K; Tanner, C M et al. (2011) Association of DRD2 and DRD3 polymorphisms with Parkinson's disease in a multiethnic consortium. J Neurol Sci 307:22-9
Popat, R A; Van Den Eeden, S K; Tanner, C M et al. (2011) Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's disease. Eur J Neurol 18:756-65
Shino, Michael Y; McGuire, Valerie; Van Den Eeden, Stephen K et al. (2010) Familial aggregation of Parkinson's disease in a multiethnic community-based case-control study. Mov Disord 25:2587-94
Lo, Raymond Y; Tanner, Caroline M; Van Den Eeden, Stephen K et al. (2010) Comorbid cancer in Parkinson's disease. Mov Disord 25:1809-17
Elbaz, Alexis; Nelson, Lorene M; Payami, Haydeh et al. (2006) Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson's disease: a large-scale international study. Lancet Neurol 5:917-23
Popat, R A; Van Den Eeden, S K; Tanner, C M et al. (2005) Effect of reproductive factors and postmenopausal hormone use on the risk of Parkinson disease. Neurology 65:383-90
Van Den Eeden, Stephen K; Tanner, Caroline M; Bernstein, Allan L et al. (2003) Incidence of Parkinson's disease: variation by age, gender, and race/ethnicity. Am J Epidemiol 157:1015-22
Whittemore, A S; Nelson, L M (1999) Study design in genetic epidemiology: theoretical and practical considerations. J Natl Cancer Inst Monogr :61-9
Checkoway, H; Nelson, L M (1999) Epidemiologic approaches to the study of Parkinson's disease etiology. Epidemiology 10:327-36

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