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Aging & Neuroepidemiology Group

Etiology of Parkinson's Disease

Honglei Chen, M.D., Ph.D.
Honglei Chen, M.D., Ph.D.
Principal Investigator
Tel (919) 541-3782
Fax (301) 480-3290
P.O. Box 12233
Mail Drop A3-05
Research Triangle Park, NC 27709

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Research Summary

Honglei Chen, M.D., Ph.D., is the head of the Aging and Neuroepidemiology Group and holds a secondary appointment in the NIEHS Neurobiology Laboratory. His group studies how environmental and genetic factors affect the risks of age-related neurodegenerative diseases and the aging process in general.

Neurodegenerative diseases are substantial public health problems in the U.S. About 5-8 percent of elderly Americans have dementia and about 1 percent have Parkinson’s disease. Understanding the causes of these diseases is crucial for prevention. Therefore, Chen’s research aims to ascertain the environmental and genetic causes of Parkinson’s disease and to characterize high risk population through research on non-motor symptoms and biomarkers. The ultimate goal is disease prevention and more effective clinical management.

Chen’s current work focuses on Parkinson’s disease, which affects over 1 million older adults in the U.S., and on several large prospective cohorts with varying emphases on Parkinson’s epidemiology.

Chen’s primary research interests include:

  • Environment, Genes, and Gene-environment interactions in the etiology of Parkinson’s disease: Genes and environmental factors, alone or in combination, contribute to the pathogenesis of Parkinson’s disease. Over the past several years, his research has contributed to a better understanding of the role of environmental factors in Parkinson’s etiology. For example, he reported that long duration of smoking, rather than smoking intensity, might underlie the lower risk of Parkinson’s disease among smokers (Chen et al., Neurology 2010). He and collaborators also found that moderate to vigorous exercise (Xu et al., Neurology 2010), ibuprofen use (Chen et al., Neurology 2003 & Annals Neurol 2005; Gao et al., Neurology 2011), and higher plasma urate (Chen et al., Am J Epidemiol 2009) were each associated with a lower risk of Parkinson’s disease. In collaboration with an international consortium and others, he contributed to the identification of multiple genetic loci that affected the risk of late-onset Parkinson’s disease (Simón-Sánchez et al., Nat Genet 2009;  IPDGC, Lancet 2011) and the first gene-environment interaction that was identified in a genome-wide approach (Hemza et al., PLoS Genet 2011).   
  • Pre-diagnostic non-motor symptoms in Parkinson’s disease: Parkinson clinical diagnosis relies on the presence of motor dysfunction, which does not become apparent until ~50% of the dopaminergic neurons in substantia nigra have died. This may partially explain the failure of neuro-protection or disease modification trials for Parkinson’s disease that all intervene after diagnosis. Over the past decade, it has become clear that Parkinson’s patients also suffer from a variety of non-motor symptoms, and some (e.g. smell loss, daytime sleepiness) may predate Parkinson’s clinical motor onset. Dr. Chen’s group therefore is working on characterizing these symptoms in older adults with the hope to identify a pre-diagnostic window where disease modification may be more realistic. He and collaborators have reported that depression (Fang et al., Mov Disord 2010), daytime sleepiness (Gao et al., Am J Epidemiol  2011), constipation (Gao et al., Am J Epidemiol 2011), and erectile dysfunction (Gao et al., Am J Epidemiol 2007) were associated with future risk of Parkinson’s disease mostly in a time dependent manner.  In the future, Dr. Chen plans to evaluate more systematically non-motor symptoms alone or in combination in relation to Parkinson’s diagnosis and how environment and genetic factors may alter the progression from preclinical to clinical Parkinson’s disease.

Dr. Chen earned his M.D. from TianJin Medical University in TianJin, China, and Master’s degree from the Chinese Academy of Preventive Medicine in BeiJing, China. In 2001, he earned his Ph.D. in Nutritional Epidemiology from Tufts University in Boston, MA and then worked as a Research Fellow and Instructor at the Harvard School of Public Health. He joined the NIEHS Epidemiology Branch as a Tenure-Track Investigator in 2005.


  • Parkinson’s, Genes and Environment (PAGE) study
    The PAGE study was built based on the large prospective NIH-AARP Diet and Health Cohort and is one of the largest epidemiological studies to date on Parkinson’s disease. The study aims to investigate the roles of diet, lifestyle, other environmental factors, and genes in Parkinson’s disease and their potential interactions in causing the illness.
  • Parkinson’s Research in the Atherosclerosis Risk In Communities (ARIC) Study  
    The goals of this study include 1) to better understand non-motor symptoms of neurodegeneration, and 2) to evaluate environmental and genetic risk factors for Parkinson’s disease, focusing on prospective biomarkers.
  • Shanghai Parkinson’s Study
    This project is being built based on the Shanghai Women’s Health Study. Dr. Chen’s group is working with this unique population to understand genetic and environmental risk factors for Parkinson’s disease among Chinese women.   
  • Parkinson’s Research in the Sister Study and the Agricultural Health Study
    The Sister Study and Agricultural Health Study are large prospective cohorts which were established and are maintained by NIEHS. In collaboration with other investigators in the Epidemiology Branch, Dr. Chen is interested in understanding non-motor symptoms in relation to Parkinson’s disease and also in evaluating the role of environment on the risk of Parkinson’s disease.  

Selected Publications

  1. Chen H, Jacobs E, Schwarzschild MA, McCullough ML, Calle EE, Thun MJ, Ascherio A. Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease. Ann Neurol. 58(6): 963-967, 2005.[Abstract]
  2. Gao X, Chen H, Schwarzschild MA, Glasser DB, Logroscino G, Rimm EB, Ascherio A: Erectile function and risk of Parkinson's disease. Am J Epidemiol 166(12):1446-50, 2007.[Abstract]
  3. Chen H, O'Reilly EJ, Schwarzschild MA, Ascherio A: Peripheral inflammatory biomarkers and risk of Parkinson's disease. Am J Epidemiol 167(1):90-5, 2008.[Abstract]
  4. Chen H, Mosley TH, Alonso A, Huang X. Plasma urate and Parkinson's disease in the Atherosclerosis Risk in Communities (ARIC) Study. Am J Epidemiol 169(9) 1064-9, 2009.[Abstract]
  5. Simón-Sánchez J, Schulte C, Bras JM, Sharma M, Gibbs JR, Berg D, Paisan-Ruiz C, Lichtner P, Scholz SW, Hernandez DG, Krüger R, Federoff M, Klein C, Goate A, Perlmutter J, Bonin M, Nalls MA, Illig T, Gieger C, Houlden H, Steffens M, Okun MS, Racette BA, Cookson MR, Foote KD, Fernandez HH, Traynor BJ, Schreiber S, Arepalli S, Zonozi R, Gwinn K, van der Brug M, Lopez G, Chanock SJ, Schatzkin A, Park Y, Hollenbeck A, Gao J, Huang X, Wood NW, Lorenz D, Deuschl G, Chen H, Riess O, Hardy JA, Singleton AB, Gasser T: Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nature Genetics 41(12):1308-12, 2009   [Abstract]
  6. Chen H, Huang X, Guo X, Mailman RB, Park Y, Kamel F, Umbach DM, Xu Q, Hollenbeck A, Schatzkin A, Blair A: Smoking duration, intensity and Parkinson’s disease. Neurology 74 (11): 878-84, 2010.[Abstract]
  7. Fang F, Xu Q, Park Y, Huang X, Hollenbeck A, Blair A, Schatzkin A, Kamel F, Chen H: Depression and the subsequent risk of Parkinson’s disease in the NIH-AARP Diet and Health Study. Movement disorders: official journal of the Movement Disorder Society 25(9):1157-62, 2010.[Abstract]
  8. Xu Q, Huang X, Park Y, Hollenbeck A, Blair A, Schatzkin A, Chen H: Physical activity and future risk of Parkinson’s disease. Neurology 75(4):341-8, 2010   [Abstract]
  9. Gao J, Huang X, Park Y, Hollenbeck A, Blair A, Schatzkin A, Chen H: Daytime napping, nighttime sleeping, and Parkinson disease. Am J Epidemiol 173(9):1032-8, 2011.[Abstract]
  10. Gao X, Chen H, Schwarzschild MA, Ascherio A: A prospective study of bowel movement frequency and risk of Parkinson’s disease. Am J Epidemiol 174(5):546-51, 2011.[Abstract]
  11. Xu Q, Park Y, Huang X, Hollenbeck A, Blair A, Schatzkin A, Chen H: Diabetes and risk of Parkinson’s disease. Diabetes Care; 34(4):910-5, 2011.[Abstract]
  12. Liu R, Gao X, Lu Y, Chen H: Meta-analysis of the relationship between Parkinson disease and melanoma. Neurology 76 (23): 2002-09, 2011  [Abstract]
  13. Gao J, Huang X, Park Y, Liu R, Mailman R, Hollenbeck A, Blair A, Schatzkin A, Chen H: ApoE genotypes and the risk for Parkinson’s disease. Neurobio Aging 32(11):2106.e1-6, 2011.[Abstract]
  14. International Parkinson Disease Genomics Consortium: Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet 377(9766): 641-9, 2011.[Abstract]
  15. Gao X, Chen H, Schwarzschild MA, Ascherio A: Use of ibuprofen and risk of Parkinson disease. Neurology 76(10):863-9, 2011.[Abstract]
  16. Hamza TH, Chen H, Hill-Burns EM, Rhodes SL, Montimurro J, Kay DM, Tenesa A, Kusel VI, Sheehan P, Eaaswarkhanth M, Yearout D, Roberts J, Agarwal  P, Bordelon Y, Park Y, Wang L, Gao J, Vance JM, Kendler KS, Scott W, Ritz B, Nutt J, Factor SA, Zabetian CP, Payami H: Genome-Wide Gene-Environment Study Identifies Glutamate Receptor Gene GRIN2A as a Parkinson’s Disease Modifier Gene via Interaction with Coffee. PLoS Genet 7(8):e1002237, 2011[Abstract]
  17. Liu R, Guo X, Park Y, Huang X, Sinha R, Freedman ND, Hollenbeck A, Blair A, Chen H: Caffeine Intake, Smoking, and Risk of Parkinson Disease in Men and Women. Am J Epidemiol: 175(11):1200-7, 2012.
  18. Fang F, Wirdefeldt K, Jacks A, Kamel F, Ye W, Chen H: CNS Infections, sepsis, and the risk for Parkinson’s disease. Int J Epidemiol 41(4):1042-9, 2012.
  19. Rinsky JL, Hoppin JA, Blair A, He K, Beane Freeman LE, Chen H. Agricultural exposures and stroke mortality in the Agricultural Health Study. Journal of toxicology and environmental health. Part A 76(13):798-814, 2013.[Abstract]

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