Research Article

Complex interactions in Parkinson's disease: A two-phased approach

  1. Demetrius M. Maraganore MD1,*,
  2. Mariza de Andrade PhD2,
  3. Timothy G. Lesnick MS2,
  4. Matthew J. Farrer PhD3,
  5. James H. Bower MD1,
  6. John A. Hardy PhD4,
  7. Walter A. Rocca MD, MPH1,2

Article first published online: 18 MAR 2003

DOI: 10.1002/mds.10431

Issue

Movement Disorders

Movement Disorders

Volume 18, Issue 6, pages 631–636, June 2003

Additional Information

How to Cite

Maraganore, D. M., de Andrade, M., Lesnick, T. G., Farrer, M. J., Bower, J. H., Hardy, J. A. and Rocca, W. A. (2003), Complex interactions in Parkinson's disease: A two-phased approach. Mov. Disord., 18: 631–636. doi: 10.1002/mds.10431

Author Information

  1. 1

    Department of Neurology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA

  2. 2

    Department of Health Sciences Research, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA

  3. 3

    Department of Neuroscience, Mayo Clinic and Mayo Foundation, Jacksonville, Florida, USA

  4. 4

    Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA

*Department of Neurology, Mayo Clinic and Mayo Foundation, 200 First Street S.W., Rochester, MN 55905

Publication History

  1. Issue published online: 28 MAY 2003
  2. Article first published online: 18 MAR 2003
  3. Manuscript Accepted: 7 NOV 2002
  4. Manuscript Revised: 10 OCT 2002
  5. Manuscript Received: 3 JUL 2002

Funded by

  • National Institute of Environmental Health Sciences. Grant Number: ES10751
  • National Institute of Neurological Disorders and Stroke. Grant Numbers: NS33978, NS40256
  • Mayo Foundation

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (78K)

Keywords:

  • Parkinson's disease;
  • susceptibility genes;
  • ubiquitin proteasome system;
  • recursive partitioning;
  • epistasis;
  • interactions

Abstract

The identification of pathogenic mutations in the three genes α-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) has elucidated the ubiquitin proteasome system (UPS) and its potential role as a causal pathway in Parkinson's disease (PD). In addition, polymorphisms of these three genes have been shown to be independently associated with PD. In a sample of 298 unrelated PD cases and 185 controls, we applied a two-phased approach of recursive partitioning and logistic regression analyses to explore complex interactions. For women only, we observed an epistatic interaction of UCHL1 and α-synuclein genotypes with significant effects on PD risk (odds ratio = 2.42; P = 0.003). Our findings are consistent with the hypothesis that PD is a multigenic disorder of the UPS. © 2003 Movement Disorder Society

View Full Article (HTML) Get PDF (78K)