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dc.contributor.authorInternational Parkinson's Disease Genomics Consortium (IPDGC); Wellcome Trust Case Control Consortium 2 (WTCCC2).
dc.contributor.authorJonsson, Palmi V
dc.contributor.authorSveinbjornsdottir, Sigurlaug
dc.date.accessioned2012-06-08T11:22:52Z
dc.date.available2012-06-08T11:22:52Z
dc.date.issued2011-06
dc.date.submitted2012-06-08
dc.identifier.citationPLoS Genet. 2011, 7(6):e1002142en_GB
dc.identifier.issn1553-7404
dc.identifier.pmid21738488
dc.identifier.doi10.1371/journal.pgen.1002142
dc.identifier.urihttp://hdl.handle.net/2336/228055
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field.en_GB
dc.description.abstractA previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p<5×10(-10), PARK16/1q32, STX1B/16p11, FGF20/8p22, STBD1/4q21, and GPNMB/7p15). Two of these five loci have been suggested by previous association studies (PARK16/1q32, FGF20/8p22), and this study provides further support for these findings. Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci.
dc.description.sponsorshipWellcome Trust/MRC WT089698 Department of Health NIHR Biomedical Research Centre Parkinson's UK 8047 J-0804 Medical Research Council G0700943 Wellcome Trust 085475/B/08/Z 085475/Z/08/Z Wolfson-Royal Society UK Medical Research Council G0901254 Reta Lila Weston Trust for Medical Research Landspitali University Hospital Icelandic Research Council European Community PIAP-GA-2008-230596 MarkMD National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services Z01 AG000949-02 Z01-ES101986 US Department of Defense W81XWH-09-2-0128 National Institutes of Health NS057105 RR024992 American Parkinson Disease Association (APDA) Barnes Jewish Hospital Foundation ForschungszentrumfurUmwelt und Gesundheit (GSF) German Federal Ministry of Education, Science, Research, and Technology State of Bavaria German National Genome Network (NGFNplus) 01GS08134 German Federal Ministry of Education and Research (BMBF) NGFN 01GR0468 Helmholtz Association HA-215 French National Agency of Research ANR-08-MNP-012 National Research Funding Agency ANR-08-NEUR-004-01en_GB
dc.language.isoenen
dc.publisherPublic Library of Scienceen_GB
dc.relation.urlhttp://dx.doi.org/10.1371/journal.pgen.1002142en_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128098/?tool=pubmeden_GB
dc.rightsArchived with thanks to PLoS geneticsen_GB
dc.subject.meshBrainen_GB
dc.subject.meshDNA Methylationen_GB
dc.subject.meshGene Expression Profilingen_GB
dc.subject.meshGene Expression Regulationen_GB
dc.subject.meshGenetic Locien_GB
dc.subject.meshGenetic Predisposition to Diseaseen_GB
dc.subject.meshGenome-Wide Association Studyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshParkinson Diseaseen_GB
dc.subject.meshPolymorphism, Single Nucleotideen_GB
dc.subject.meshRisk Assessmenten_GB
dc.titleA two-stage meta-analysis identifies several new loci for Parkinson's disease.en
dc.typeArticleen
dc.identifier.journalPLoS geneticsen_GB
html.description.abstractA previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p<5×10(-10), PARK16/1q32, STX1B/16p11, FGF20/8p22, STBD1/4q21, and GPNMB/7p15). Two of these five loci have been suggested by previous association studies (PARK16/1q32, FGF20/8p22), and this study provides further support for these findings. Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci.


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