Parkinsons disease (PD) is the second most prevalent neurodegenerative disease and affects more than one million elderly Americans. As the population ages, the burden of PD is expected to increase. Although there are effective measures to control the symptoms of PD, patients eventually develop severe physical and mental disabilities and often die of complications.
My research aims to ascertain the environmental and genetic causes of PD and to characterize high-risk populations through research on pre-motor symptoms and biomarkers. Genes and environmental factors, alone or in combination, contribute to PD development. Over years, our research has contributed to a better understanding of the role of environmental factors in Parkinsons etiology, for example, on smoking, coffee drinking, infections, and use of certain medications. In the past year, we investigated some other potential risk factors for PD. Using data from the Parkinsons Genes and Environmental Studies, we prospectively investigated the association between alcohol drinking and future PD risk. We found that while moderate beer drinking was associated a lower risk for PD, liquor drinking was associated with a higher risk (PLoS One, 2013). Using data from the Swedish Patient Registry, we found that recent head injury was not related to a higher risk of PD (Mov Disord 2013). In the past, we have reported that higher plasma urate was associated with a lower risk of PD;we examined last year whether this association could be attributed to known genetic variants that are associated with plasma urate. We did not find a link between these genetic variants and PD (Transl Neurodegener, 2013). In addition, we are also part of a larger consortium to search for genetic causes of PD (e.g. Hum Mol Genet, 2012, 2013;PLoS Med 2013). Another important area of my research is the epidemiology of PD pre-motor symptoms. Clinicians and scientists have known for years that in addition to the characteristic motor signs, PD patients suffer from non-motor symptoms ranging from hyposmia (poor sense of smell) to dementia and psychosis. Although these symptoms can develop both before and after the clinical diagnosis of PD, I am interested in several symptoms that may develop prior to disease diagnosis by years. Examples of these symptoms include hyposmia, constipation, depression and certain sleep disturbances. These pre-motor symptoms may greatly facilitate research to identify populations at higher risk for PD and to understand early PD etiology. In the past, we have examined several individual symptoms in relation to PD risk. I am now conducting epidemiological studies to better characterize pre-motor symptoms in various populations and to understand their relevance to the natural history and etiology of PD. Our specific hypotheses are that 1) the presence of multiple pre-motor symptoms in the same individual predicts higher risk of PD;2) environmental (e.g. smoking, caffeine intake, pesticide exposure, ibuprofen use) and genetic (e.g. SNCA, MAPT) factors affect the presence of these pre-motor symptoms and/or modify their progression to overt PD. We have summarized these ideas in a recent paper on the journal of Environmental Health Perspectives. I am the principal Investigator on several PD studies that were built on large prospective cohorts. I have focused on prospective cohorts over case-control studies because they are relatively less prone to recall bias and reverse causation. Since PD is a rare outcome, large cohorts and long follow-up times are needed;research built on existing cohorts allows for relatively efficient and cost-effective case-identification. Further, by its nature, pre-motor research requires prospective studies. My ongoing projects include the Parkinsons Genes and Environment Study based on the NIH-AARP Diet and Health cohort, the PD project in the Atherosclerosis Risk In Communities study, and the Shanghai Parkinsons Study in the Shanghai Womens Health Study. Further, in collaboration with Branch colleagues, I am developing PD research in the Agricultural Health Study and the Sister Study. Finally, I have been continuing a longstanding collaboration with colleagues from the Harvard School of Public Health, and have developed a new collaboration with investigators at the Karolinska Institute. While these studies have different specific foci, they share a common theme of revealing the causes of PD and characterizing high risk populations for the purpose of disease prevention. In addition to PD research, I am also a member of the Global Burden of Disease group that estimated the public health burdens of a wide range of diseases across countries in the world. Primary findings were published in a series of papers on Lancet and JAMA.

Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2013
Total Cost
$1,028,725
Indirect Cost
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State
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Dong, Jing; Wyss, Annah; Yang, Jingyun et al. (2016) 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 :
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
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
Liu, Rui; Young, Michael T; Chen, Jiu-Chiuan et al. (2016) Ambient Air Pollution Exposures and Risk of Parkinson Disease. Environ Health Perspect 124:1759-1765
Freedman, D Michal; Wu, Jincao; Chen, Honglei et al. (2016) Associations between cancer and Parkinson's disease in U.S. elderly adults. Int J Epidemiol 45:741-51
Kirrane, Ellen F; Bowman, Christal; Davis, J Allen et al. (2015) Associations of Ozone and PM2.5 Concentrations With Parkinson's Disease Among Participants in the Agricultural Health Study. J Occup Environ Med 57:509-17
Chen, Renjie; Zhao, Ang; Chen, Honglei et al. (2015) Cardiopulmonary benefits of reducing indoor particles of outdoor origin: a randomized, double-blind crossover trial of air purifiers. J Am Coll Cardiol 65:2279-87
Huang, Xuemei; Alonso, Alvaro; Guo, Xuguang et al. (2015) Statins, plasma cholesterol, and risk of Parkinson's disease: a prospective study. Mov Disord 30:552-9
Alonso, Alvaro; Huang, Xuemei; Mosley, Thomas H et al. (2015) Heart rate variability and the risk of Parkinson disease: The Atherosclerosis Risk in Communities study. Ann Neurol 77:877-83
Chen, Honglei; Zhao, Edward J; Zhang, Wen et al. (2015) Meta-analyses on prevalence of selected Parkinson's nonmotor symptoms before and after diagnosis. Transl Neurodegener 4:1

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