Complex interactions in Parkinson's disease: A two‐phased approach
Identifieur interne : 001E32 ( Istex/Corpus ); précédent : 001E31; suivant : 001E33Complex interactions in Parkinson's disease: A two‐phased approach
Auteurs : Demetrius M. Maraganore ; Mariza De Andrade ; Timothy G. Lesnick ; Matthew J. Farrer ; James H. Bower ; John A. Hardy ; Walter A. RoccaSource :
- Movement Disorders [ 0885-3185 ] ; 2003-06.
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- KwdEn :
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
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DOI: 10.1002/mds.10431
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<front><div type="abstract" xml:lang="en">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</div>
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<p>The identification of pathogenic mutations in the three genes α‐<i>synuclein</i>
, <i>parkin</i>
, and <i>ubiquitin carboxy‐terminal hydrolase L1</i>
(<i>UCHL1</i>
) 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 <i>UCHL1</i>
and α‐<i>synuclein</i>
genotypes with significant effects on PD risk (odds ratio = 2.42; <i>P</i>
= 0.003). Our findings are consistent with the hypothesis that PD is a multigenic disorder of the UPS. © 2003 Movement Disorder Society</p>
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<!--Version 0.6 générée le 4-12-2015--><mods version="3.6"><titleInfo lang="en"><title>Complex interactions in Parkinson's disease: A two‐phased approach</title>
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<name type="personal"><namePart type="given">Demetrius M.</namePart>
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<affiliation>Department of Neurology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA</affiliation>
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<name type="personal"><namePart type="given">Timothy G.</namePart>
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<name type="personal"><namePart type="given">Matthew J.</namePart>
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<namePart type="termsOfAddress">MD, MPH</namePart>
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<abstract lang="en">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</abstract>
<note type="funding">National Institute of Environmental Health Sciences - No. ES10751; </note>
<note type="funding">National Institute of Neurological Disorders and Stroke - No. NS33978; No. NS40256; </note>
<note type="funding">Mayo Foundation</note>
<subject lang="en"><genre>Keywords</genre>
<topic>Parkinson's disease</topic>
<topic>susceptibility genes</topic>
<topic>ubiquitin proteasome system</topic>
<topic>recursive partitioning</topic>
<topic>epistasis</topic>
<topic>interactions</topic>
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<identifier type="ISSN">0885-3185</identifier>
<identifier type="eISSN">1531-8257</identifier>
<identifier type="DOI">10.1002/(ISSN)1531-8257</identifier>
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<part><date>2003</date>
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