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Article scientifique
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Anglais

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

Contributeurs/tricesFrench Parkinson's Disease Genetics Study Group
Collaborateurs/tricesPollak, Pierre
Publié dansPLOS genetics, vol. 7, no. 6, e1002142
Date de publication2011
Résumé

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.

Mots-clés
  • Brain/metabolism
  • DNA Methylation
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Loci/genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Parkinson Disease/genetics
  • Polymorphism, Single Nucleotide/genetics
  • Risk Assessment
Groupe de recherche
Citation (format ISO)
French Parkinson’s Disease Genetics Study Group. A two-stage meta-analysis identifies several new loci for Parkinson’s disease. In: PLOS genetics, 2011, vol. 7, n° 6, p. e1002142. doi: 10.1371/journal.pgen.1002142
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Article (Published version)
accessLevelPublic
Identifiants
ISSN du journal1553-7390
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