Title |
UCHL1 is a Parkinson's disease susceptibility gene
|
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Published in |
Annals of Neurology, March 2004
|
DOI | 10.1002/ana.20017 |
Pubmed ID | |
Authors |
Demetrius M. Maraganore, Timothy G. Lesnick, Alexis Elbaz, Marie‐Christine Chartier‐Harlin, Thomas Gasser, Rejko Krüger, Nobutaka Hattori, George D. Mellick, Aldo Quattrone, Jun‐Ichi Satoh, Taksushi Toda, Jian Wang, John P.A. Ioannidis, Mariza de Andrade, Walter A. Rocca, the UCHL1 Global Genetics Consortium |
Abstract |
The reported inverse association between the S18Y variant of the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) gene and Parkinson's disease (PD) has strong biological plausibility. If confirmed, genetic association of this variant with PD may support molecular targeting of the UCHL1 gene and its product as a therapeutic strategy for PD. In this light, we performed a collaborative pooled analysis of individual-level data from all 11 published studies of the UCHL1 S18Y gene variant and PD. There were 1,970 cases and 2,224 unrelated controls. We found a statistically significant inverse association of S18Y with PD. Carriers of the variant allele (Y/Y plus Y/S vs S/S) had an odds ratio (OR) of 0.84 (95% confidence interval [CI], 0.73-0.95) and homozygotes for the variant allele (Y/Y vs S/S plus Y/S) had an OR of 0.71 (95% CI, 0.57-0.88). There was a linear trend in the log OR consistent with a gene dose effect (p = 0.01). The inverse association was most apparent for young cases compared with young controls. There was no evidence for publication bias and the associations remained significant after excluding the first published, hypothesis-generating study. These findings confirm that UCHL1 is a susceptibility gene for PD and a potential target for disease-modifying therapies. |
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Denmark | 2 | 100% |
Demographic breakdown
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
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Germany | 4 | 3% |
France | 2 | 2% |
United States | 1 | <1% |
Unknown | 118 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 28 | 22% |
Student > Bachelor | 20 | 16% |
Student > Master | 17 | 14% |
Researcher | 12 | 10% |
Student > Postgraduate | 7 | 6% |
Other | 23 | 18% |
Unknown | 18 | 14% |
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Medicine and Dentistry | 20 | 16% |
Biochemistry, Genetics and Molecular Biology | 16 | 13% |
Neuroscience | 13 | 10% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 2% |
Other | 11 | 9% |
Unknown | 24 | 19% |