Show simple item record

dc.contributor.authorMaraganore, Demetrius M
dc.contributor.authorde Andrade, Mariza
dc.contributor.authorElbaz, Alexis
dc.contributor.authorFarrer, Matthew J
dc.contributor.authorIoannidis, John PA
dc.contributor.authorKrueger, Rejko
dc.contributor.authorRocca, Walter A
dc.contributor.authorSchneider, Nicole K
dc.contributor.authorLesnick, Timothy G
dc.contributor.authorLincoln, Sarah J
dc.contributor.authorHulihan, Mary M
dc.contributor.authorAasly, Jan O
dc.contributor.authorAshizawa, Tetsuo
dc.contributor.authorChartier-Harlin, Marie-Christine
dc.contributor.authorCheckoway, Harvey
dc.contributor.authorFerrarese, Carlo
dc.contributor.authorHadjigeorgiou, Georgios
dc.contributor.authorHattori, Nobutaka
dc.contributor.authorKawakami, Hideshi
dc.contributor.authorLambert, Jean-Charles
dc.contributor.authorLynch, Timothy
dc.contributor.authorMellick, George D
dc.contributor.authorPapapetropoulos, Spiridon
dc.contributor.authorParsian, Abbas
dc.contributor.authorQuattrone, Aldo
dc.contributor.authorRiess, Olaf
dc.contributor.authorTan, Eng-King
dc.contributor.authorVan Broeckhoven, Christine
dc.contributor.editorCatherine D DeAngelis
dc.date.accessioned2017-05-03T14:29:01Z
dc.date.available2017-05-03T14:29:01Z
dc.date.issued2006
dc.identifier.issn0098-7484
dc.identifier.doi10.1001/jama.296.6.661
dc.identifier.urihttp://hdl.handle.net/10072/14359
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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Medical Association
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom661
dc.relation.ispartofpageto670
dc.relation.ispartofissue6
dc.relation.ispartofjournalJournal of American Medical Association
dc.relation.ispartofvolume296
dc.rights.retentionY
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchcode32
dc.titleCollaborative Analysis of alpha-Synuclein Gene Promoter Variability and Parkinson Disease
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2015-06-01T23:37:10Z
gro.hasfulltextNo Full Text
gro.griffith.authorMellick, George


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record