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Complex interactions in Parkinson's disease: A two‐phased approach
Author(s) -
Maraganore Demetrius M.,
de Andrade Mariza,
Lesnick Timothy G.,
Farrer Matthew J.,
Bower James H.,
Hardy John A.,
Rocca Walter A.
Publication year - 2003
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.10431
Subject(s) - parkinson's disease , degenerative disease , neuroscience , disease , central nervous system disease , physical medicine and rehabilitation , medicine , psychology
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