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dc.contributor.authorM. Maraganore, Demetriusen_US
dc.contributor.authorAndrade, Marizaen_US
dc.contributor.authorElbaz, Alexisen_US
dc.contributor.authorJ. Farrer, Matthewen_US
dc.contributor.authorP. Ioannidis, Johnen_US
dc.contributor.authorKruger, Rejkoen_US
dc.contributor.authorA. Rocca, Walteren_US
dc.contributor.authorK. Schneider, Nicoleen_US
dc.contributor.authorG.Lesnick, Timothyen_US
dc.contributor.authorJ. Lincoln, Sarahen_US
dc.contributor.authorM. Hulihan, Maryen_US
dc.contributor.authorO. Aasly, Janen_US
dc.contributor.authorAshizawa, Tetsuoen_US
dc.contributor.authorChartier-Harlin, Marie-Christineen_US
dc.contributor.authorCheckoway, Harveyen_US
dc.contributor.authorFerrarese, Carloen_US
dc.contributor.authorHadjigeorgiou, Georgiosen_US
dc.contributor.authorHattori, Nobutakaen_US
dc.contributor.authorKawakami, Hideshien_US
dc.contributor.authorLambert, Jean-Charlesen_US
dc.contributor.authorLynch, Timothyen_US
dc.contributor.authorMellick, Georgeen_US
dc.contributor.authorPapapetropoulos, Spiridonen_US
dc.contributor.authorParsian, Abbasen_US
dc.contributor.authorQuattrone, Aldoen_US
dc.contributor.authorRiess, Olafen_US
dc.contributor.authorTan, Eng-Kingen_US
dc.contributor.authorVan Broeckhoven, Christineen_US
dc.contributor.editorCatherine D DeAngelisen_US
dc.description.abstractContext Identification and replication of susceptibility genes for Parkinson disease at the population level have been hampered by small studies with potential biases. -Synuclein (SNCA) has been one of the most promising susceptibility genes, but large-scale studies have been lacking. Objective To determine whether allele-length variability in the dinucleotide repeat sequence (REP1) of the SNCA gene promoter is associated with Parkinson disease susceptibility, whether SNCA promoter haplotypes are associated with Parkinson disease, and whether REP1 variability modifies age at onset. Design, Setting, and Participants We performed a collaborative analysis of individual-level data on SNCA REP1 and flanking markers in patients with Parkinson disease and controls. Study site recruitment, data collection, and analyses were performed between April 5, 2004, and December 31, 2005. Eighteen participating sites of a global genetics consortium provided clinical data. Genotyping was performed for SNCA REP1, -770, and -116 markers at individual sites; however, each site also provided 20 DNA samples for regenotyping centrally. Main Outcome Measures Measures included estimations of Hardy-Weinberg equilibrium in controls; a test of heterogeneity; analyses for association of single variants or haplotypes; and survival analyses for age at onset. Results Of the 18 sites, 11 met stringent criteria for concordance with Hardy-Weinberg equilibrium and low genotyping error rate. These 11 sites provided complete data for 2692 cases and 2652 controls. There was no heterogeneity across studies (P>.60). The SNCA REP1 alleles differed in frequency for cases and controls (P<.001). Genotypes defined by the 263 base-pair allele were associated with Parkinson disease (odds ratio, 1.43; 95% confidence interval, 1.22-1.69; P<.001 for trend). Multilocus haplotypes differed in frequency for cases and controls (global score statistic, P<.001). Two-loci haplotypes were associated with Parkinson disease only when they included REP1 as one of the loci. However, genotypes defined by REP1 alleles did not modify age at onset (P = .55). Conclusion This large-scale collaborative analysis demonstrates that SNCA REP1 allele-length variability is associated with an increased risk of Parkinson disease.en_US
dc.publisherAmerican Medical Associationen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofjournalJournal of American Medical Associationen_US
dc.titleCollaborative Analysis of alpha-Synuclein Gene Promoter Variability and Parkinson Diseaseen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.hasfulltextNo Full Text

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