Gene-environment interactions may be major contributors to Parkinson's disease (PD) etiology, however this area of research has been severely hampered by the relatively small sample size of most population-based PD studies and/or a lack of valid and standardized exposure assessment across studies. We will take advantage of a worldwide unique resource available in Denmark to conduct the largest population-based case-control study ever to examine gene-environment interactions in PD: the National Parkinson's Patient Register in Denmark. We propose to recruit actively and prospectively approximately 2500 recently registered incident PD patients and 2,500 age-gender matched controls from the Danish population to collect risk factor information per interview and biological materials for genetic analyses. All patients will be examined and characterized clinically and phenotypically by a trained movement disorder fellow. We will examine 1) which lifetime occupations and occupational exposures are associated with PD;specifically, we will evaluate farming and greenhouse occupations (pesticides), metal related industries (metals and solvents), and night shift work (melatonin levels);2) whether certain drugs and medical conditions are positively or inversely associated with PD (e.g. NSAIDS, aspirin, and cortisone use, or M. Crohn and colitis and rheumatoid arthritis) through their potential to induce chronically low iron levels and induce/reduce systemic inflammation;and 3) previously identified factors including smoking, alcohol use, dietary nutrients and contaminants (such as pesticides and metals from fish consumption), and physical activity. Most importantly, we will examine whether functional polymorphisms of metabolic and PD specific candidate genes differentially influence risks associated with environmental factors. As a secondary aim we will also employ passive record linkage by unique ID to link data from the National Patient Register, Pharmacy Database, and National Pension fund to identify risk factor information contained in these records (e.g. occupations, medication use, and diseases prior to PD onset) for approximately 13,000 PD cases diagnosed since 1983 and age-gender matched controls from the Danish population. The proposed research cannot be performed in the US due to a lack of population PD registries that would provide access to such a large number of cases and valid methods for control recruitment from the general population.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES013717-04
Application #
7676080
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Lawler, Cindy P
Project Start
2006-09-19
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
4
Fiscal Year
2009
Total Cost
$923,322
Indirect Cost
Name
University of California Los Angeles
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Chen, Honglei; Ritz, Beate (2018) The Search for Environmental Causes of Parkinson's Disease: Moving Forward. J Parkinsons Dis 8:S9-S17
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Shih, I-Fan; Starhof, Charlotte; Lassen, Christina Funch et al. (2017) Occupational and recreational physical activity and Parkinson's disease in Denmark. Scand J Work Environ Health 43:210-216
Chuang, Yu-Hsuan; Lill, Christina M; Lee, Pei-Chen et al. (2016) Gene-Environment Interaction in Parkinson's Disease: Coffee, ADORA2A, and CYP1A2. Neuroepidemiology 47:192-200
Ritz, Beate; Lee, Pei-Chen; Hansen, Johnni et al. (2016) Traffic-Related Air Pollution and Parkinson's Disease in Denmark: A Case-Control Study. Environ Health Perspect 124:351-6
Schernhammer, Eva S; Lassen, Christina F; Kenborg, Line et al. (2015) Occupational history of night shift work and Parkinson's disease in Denmark. Scand J Work Environ Health 41:377-83
Lill, Christina M; Hansen, Johnni; Olsen, Jørgen H et al. (2015) Impact of Parkinson's disease risk loci on age at onset. Mov Disord 30:847-50
Wermuth, Lene; Cui, Xin; Greene, Naomi et al. (2015) Medical Record Review to Differentiate between Idiopathic Parkinson's Disease and Parkinsonism: A Danish Record Linkage Study with 10 Years of Follow-Up. Parkinsons Dis 2015:781479
Lill, Christina M; Rengmark, Aina; Pihlstrøm, Lasse et al. (2015) The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease. Alzheimers Dement 11:1407-1416
Kenborg, Line; Lassen, Christina F; Ritz, Beate et al. (2015) Lifestyle, family history, and risk of idiopathic Parkinson disease: a large Danish case-control study. Am J Epidemiol 181:808-16

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