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

doi:10.1002/mds.10431

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 journal › Article › peer-review

28 Scopus citations

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.

Original language	English (US)
Pages (from-to)	631-636
Number of pages	6
Journal	Movement Disorders
Volume	18
Issue number	6
DOIs	https://doi.org/10.1002/mds.10431
State	Published - Jun 1 2003

Keywords

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

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/mds.10431

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title = "Complex interactions in Parkinson's disease: A two-phases approach",

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.",

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AU - de Andrade, Mariza

AU - Lesnick, Timothy G.

AU - Farrer, Matthew J.

AU - Bower, James H.

AU - Hardy, John A.

AU - Rocca, Walter A.

PY - 2003/6/1

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KW - Interactions

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KW - Recursive partitioning

KW - Susceptibility genes

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

Abstract

Keywords

ASJC Scopus subject areas

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