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Meta-Analysis
. 2011 Jun;7(6):e1002142.
doi: 10.1371/journal.pgen.1002142. Epub 2011 Jun 30.

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

International Parkinson's Disease Genomics Consortium (IPDGC); Wellcome Trust Case Control Consortium 2 (WTCCC2)
Collaborators
Meta-Analysis

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

International Parkinson's Disease Genomics Consortium (IPDGC) et al. PLoS Genet. 2011 Jun.

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Forest plots detailing effect estimates from the combined analysis of all data contributed by the International Parkinson Disease Genomics Consortium (joint estimates describing constituent effects of Stage 1+Stage 2).
See this image and copyright information in PMC

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