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

A two-stage meta-analysis identifies several new loci for Parkinson's disease
A two-stage meta-analysis identifies several new loci for Parkinson's disease
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.
1553-7390
1-9
Morrison, Karen
f00890f0-2fde-4dbd-a73b-7422e1b0ede8
Morrison, Karen
f00890f0-2fde-4dbd-a73b-7422e1b0ede8

Morrison, Karen (2011) A two-stage meta-analysis identifies several new loci for Parkinson's disease. PLoS Genetics, 7 (6), 1-9. (doi:10.1371/journal.pgen.1002142).

Record type: Article

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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Accepted/In Press date: 8 April 2011
Published date: 30 June 2011
Additional Information: International Parkinson's Disease Genomics Consortium (IPDGC), Wellcome Trust Case Control Consortium 2 (WTCCC2)
Organisations: Medical Education

Identifiers

Local EPrints ID: 398758
URI: http://eprints.soton.ac.uk/id/eprint/398758
ISSN: 1553-7390
PURE UUID: 772ba853-34d8-41b7-b8dd-40f4e1652be3
ORCID for Karen Morrison: ORCID iD orcid.org/0000-0003-0216-5717

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Date deposited: 01 Aug 2016 13:30
Last modified: 17 Dec 2019 01:32

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