Parkinsons disease (PD) is the second most prevalent neurodegenerative disease in the elderly population and its causes are largely unknown. Although several genes have been identified to be responsible for some of the early onset familial cases, the causes of most PD cases remained unexplained. Epidemiological studies on PD environmental risk factors are proved difficult, due to the low incidence, the insidious onset and the clinical course of the disease.? ? In collaboration with Dr. Alberto Ascherios group at Harvard School of Public Health, I have been investigating dietary and lifestyle risk factors in relation to PD risk in three well established prospective cohorts: the Health Professionals Follow-up Study, the Nurses Health Study, and the Cancer Prevention Study II Nutrition Cohort from American Cancer Society. The prospective design is important in PD epidemiological research as it avoids many of the potential biases that the previous case-control studies had. Further, these three cohrots are to date the largest prospective studies on PD and have generated some interesting results that need to be validated in future investigations. Consistent findings from these studies included a positive association between dairy consumption and risk of PD and an inverse association between non-aspirin NSAIDs use and PD risk. Recently, we were also able to provide to date the strongest prospective evidence linking pesticide use and a higher PD risk.? ? Further, I am also developing a new research project on PD (the Parkinsons Genes and Environment Study (PAGE)) to investigate environmental and genetic risk factors for PD in the NIH-AARP Diet and Health Study, which is a large prospective cohort that was initiated in mid-1990s by Dr. Arthur Schatzkin at NCI for cancer research. Over half a million US men and women 50 years or older participated in the baseline surveys in 1995 and 1996 and a follow-up survey is now underway to document the occurrence of chronic diseases, including PD. Therefore, this cohort provides an excellent infrastructure for PD research. ? ? The PAGE study includes two phases: PAGE 1 is a longitudinal study to investigate whether diet/lifestyle are related to PD risk, using exposure information collected at baseline and PD cases identified in the follow-up. PAGE 2 will be a case-control study to examine other environmental/occupational risk factors in relation to PD and will require further retrospective exposure data collection from both cases and selected controls. For both projects, the key is to do an accurate diagnostic confirmation of PD cases, and an intrinsic component of both projects is DNA collection, which will allow us to conduct case-control analyses of diet-gene / environment-gene interactions. Therefore, PD diagnostic confirmation and DNA collection will be carried out as part of PAGE 1. In PAGE2, we will conduct retrospective data collection using computer assisted telephone interview (CATI). Of particular interest are exposures to pesticides, heavy metals, medication, and history of infectious diseases. ? ? Eventually, we expect to confirm approximately 1,000 incident PD cases (1996-2004) based on the age- and gender-specific incidence from other large prospective cohorts with similar design. This will make the study the largest longitudinal study on PD to date and thus contribute significantly to our understanding of the environmental and genetic causes of late onset sporadic PD.? ? We started data collection for PAGE I project this year and plan to finish it later next year. During the same time, we plan to launch the PAGE II project.? ? In addition to these projects, I am also working on a few smaller projects on PD and related neurodegenerative conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES101986-02
Application #
7594019
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2007
Total Cost
$336,133
Indirect Cost
City
State
Country
United States
Zip Code
Palta, Priya; Chen, Honglei; Deal, Jennifer A et al. (2018) Olfactory function and neurocognitive outcomes in old age: The Atherosclerosis Risk in Communities Neurocognitive Study. Alzheimers Dement 14:1015-1021
Noyce, Alastair J; Kia, Demis A; Hemani, Gibran et al. (2017) Estimating the causal influence of body mass index on risk of Parkinson disease: A Mendelian randomisation study. PLoS Med 14:e1002314
Liu, Guodong; Sterling, Nicholas W; Kong, Lan et al. (2017) Statins may facilitate Parkinson's disease: Insight gained from a large, national claims database. Mov Disord 32:913-917
Sterling, Nicholas W; Du, Guangwei; Lewis, Mechelle M et al. (2017) Cortical gray and subcortical white matter associations in Parkinson's disease. Neurobiol Aging 49:100-108
Dong, Jing; Wyss, Annah; Yang, Jingyun et al. (2017) Genome-Wide Association Analysis of the Sense of Smell in U.S. Older Adults: Identification of Novel Risk Loci in African-Americans and European-Americans. Mol Neurobiol 54:8021-8032
Giri, Anamika; Mok, Kin Y; Jansen, Iris et al. (2017) Lack of evidence for a role of genetic variation in TMEM230 in the risk for Parkinson's disease in the Caucasian population. Neurobiol Aging 50:167.e11-167.e13
Jansen, Iris E; Ye, Hui; Heetveld, Sasja et al. (2017) Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing. Genome Biol 18:22
Liu, Bojing; Chen, Honglei; Fang, Fang et al. (2016) Early-Life Factors and Risk of Parkinson's Disease: A Register-Based Cohort Study. PLoS One 11:e0152841
Lubbe, Steven J; Escott-Price, Valentina; Gibbs, J Raphael et al. (2016) Additional rare variant analysis in Parkinson's disease cases with and without known pathogenic mutations: evidence for oligogenic inheritance. Hum Mol Genet 25:5483-5489
Shrestha, Srishti; Lutsey, Pamela L; Alonso, Alvaro et al. (2016) Serum 25-hydroxyvitamin D concentrations in Mid-adulthood and Parkinson's disease risk. Mov Disord 31:972-8

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