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A two-stage meta-analysis identifies several new loci for Parkinson's disease.
PLoS Genet. 7:e1002142 (2011)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Genome-wide association; Fibroblast-growth-factor; Alpha-synuclein; Gene; Mutations; Risk; Population; Haplotypes; Variants; Sequence
Language
english
Publication Year
2011
HGF-reported in Year
2011
ISSN (print) / ISBN
1553-7390
e-ISSN
1553-7404
Journal
PLoS Genetics
Quellenangaben
Volume: 7,
Issue: 6,
Article Number: e1002142
Publisher
Public Library of Science (PLoS)
Reviewing status
Peer reviewed
POF-Topic(s)
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-504200-003
G-500700-001
G-500700-001
PubMed ID
21738488
Erfassungsdatum
2011-09-12