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A two-stage meta-analysis identifies several new loci for Parkinson's Disease

Morris, Huw Rees, Pearson, Justin P., Williams, Nigel Melville, Wickremaratchi, Mirdhu, International Parkinson's Disease Genomics Consortium (IPDGC), and Wellcome Trust Case Control Consortium (WTCCC), 2011. A two-stage meta-analysis identifies several new loci for Parkinson's Disease. PLoS Genetics 7 (6) , e1002142. 10.1371/journal.pgen.1002142

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Abstract

A 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Public Library of Science
ISSN: 1553-7404
Date of First Compliant Deposit: 30 March 2016
Last Modified: 09 Jan 2018 20:15
URI: http://orca-mwe.cf.ac.uk/id/eprint/28761

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