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

Demetrius M. Maraganore, Mariza de Andrade, Timothy G. Lesnick, Matthew J. Farrer, James H. Bower, John A. Hardy, Walter A. Rocca

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)631-636
Number of pages6
JournalMovement Disorders
Issue number6
StatePublished - Jun 1 2003


  • Epistasis
  • Interactions
  • Parkinson's disease
  • Recursive partitioning
  • Susceptibility genes
  • Ubiquitin proteasome system

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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