Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson's disease: a large-scale international study

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Title Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson's disease: a large-scale international study
Author Elbaz, Alexis; Nelson, Lorene M.; Payami, Haydeh; Ioannidis, John P.A.; Fiske, Brian K.; Annesi, Grazia; Belin, Andrea Carmine; Factor, Stewart A.; Ferrarese, Carlo; Hadjigeorgiou, Georgios M.; Higgins, Donald S.; Kawakami, Hideshi; Kruger, Rejko; Marder, Karen S.; Mayeux, Richard P.; Mellick, George; Nutt, John G.; Ritz, Beate; Samii, Ali; Tanner, Caroline M.; Broeckhoven, Christine Van; Eeden, Stephen K. Van Den; Wirdefeldt, Karin; Zabetian, Cyrus P.; Dehem, Marie; Montimurro, Jennifer S.; Southwick, Audrey; Myers, Richard M.; Trikalinos, Thomas A.
Journal Name The Lancet Neurology
Year Published 2006
Place of publication United Kingdom
Publisher The Lancet Publishing Group / Elsevier
Abstract Background A genome-wide association study identified 13 single-nucleotide polymorphisms (SNPs) significantly associated with Parkinson's disease. Small-scale replication studies were largely non-confirmatory, but a meta-analysis that included data from the original study could not exclude all SNP associations, leaving relevance of several markers uncertain. Methods Investigators from three Michael J Fox Foundation for Parkinson's Research-funded genetics consortia—comprising 14 teams—contributed DNA samples from 5526 patients with Parkinson's disease and 6682 controls, which were genotyped for the 13 SNPs. Most (88%) participants were of white, non-Hispanic descent. We assessed log-additive genetic effects using fixed and random effects models stratified by team and ethnic origin, and tested for heterogeneity across strata. A meta-analysis was undertaken that incorporated data from the original genome-wide study as well as subsequent replication studies. Findings In fixed and random-effects models no associations with any of the 13 SNPs were identified (odds ratios 0·89 to 1·09). Heterogeneity between studies and between ethnic groups was low for all SNPs. Subgroup analyses by age at study entry, ethnic origin, sex, and family history did not show any consistent associations. In our meta-analysis, no SNP showed significant association (summary odds ratios 0·95 to 1.08); there was little heterogeneity except for SNP rs7520966. Interpretation Our results do not lend support to the finding that the 13 SNPs reported in the original genome-wide association study are genetic susceptibility factors for Parkinson's disease.
Peer Reviewed Yes
Published Yes
Publisher URI http://www.elsevier.com/wps/find/journaldescription.cws_home/622235/description#description
Alternative URI http://dx.doi.org/10.1016/S1474-4422(06)70579-8
Copyright Statement Copyright 2006 Elsevier. Please refer to the journal's website for access to the definitive, published version.
Volume 5
Issue Number 11
Page from 917
Page to 923
ISSN 1474-4422
Date Accessioned 2007-03-15
Date Available 2008-12-04T01:37:47Z
Language en_AU
Research Centre Eskitis Institute for Drug Discovery
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Central Nervous System
URI http://hdl.handle.net/10072/14358
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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