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American Journal of Epidemiology Advance Access originally published online on October 28, 2009
American Journal of Epidemiology 2009 170(11):1344-1357; doi:10.1093/aje/kwp288
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American Journal of Epidemiology Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2009.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Association Between the Ubiquitin Carboxyl-Terminal Esterase L1 Gene (UCHL1) S18Y Variant and Parkinson's Disease: A HuGE Review and Meta-Analysis

Margaret Ragland, Carolyn Hutter, Cyrus Zabetian and Karen Edwards*

* Correspondence to Dr. Karen Edwards, University of Washington, Center for Genomics and Public Health, Box 354921, 6200 NE 74th Street, Building 29, Suite 250, Seattle, WA 98115 (e-mail: keddy{at}u.washington.edu).

Received for publication December 10, 2008. Accepted for publication August 13, 2009.

The ubiquitin carboxyl-terminal esterase L1 gene, UCHL1, located on chromosome 4p14, has been studied as a potential candidate gene for Parkinson's disease risk. The authors conducted a Human Genome Epidemiology review and meta-analysis of published case-control studies of the UCHL1 S18Y variant and Parkinson's disease in Asian and Caucasian samples. The meta-analysis of studies in populations of Asian ancestry showed a statistically significant association between the Y allele and reduced risk of Parkinson's disease under a recessive model (odds ratio (OR) for YY vs. SY + SS = 0.79, 95% confidence interval (CI): 0.67, 0.94; P = 0.006). For a dominant model, the association was not significant in Asian populations (OR for YY + SY vs. SS = 0.88, 95% CI: 0.68, 1.14; P = 0.33). For populations of European ancestry, the meta-analysis showed a significant association between the Y allele and decreased risk of Parkinson's disease under a dominant model (OR = 0.89, 95% CI: 0.81, 0.98; P = 0.02) but not under a recessive model (OR = 0.92, 95% CI: 0.66, 1.30; P = 0.65). Using the Venice criteria, developed by the Human Genome Epidemiology Network Working Group on the assessment of cumulative evidence, the authors concluded that moderate evidence exists for an association between the S18Y variant and Parkinson's disease.

case-control studies; epidemiology; genes; genetics; meta-analysis; Parkinson disease; review; UCHL1

Abbreviations: CI, confidence interval; OR, odds ratio; PARK, a region identified in linkage studies of Parkinson's disease; SNP, single nucleotide polymorphism; UCHL1, ubiquitin carboxyl-terminal esterase L1

Editor's note: This paper is also available on the website of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/).


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