A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

作者：Plagnol Vincent^*; Nalls Michael A; Bras Jose M; Hernandez Dena G; Sharma Manu; Sheerin Una Marie; Saad Mohamad; Simon Sanchez Javier; Schulte Claudia; Lesage Suzanne; Sveinbjornsdottir Sigurlaug; Amouyel Philippe; Arepalli Sampath; Band Gavin; Barker Roger A; Bellinguez Celine; Ben Shlomo Yoav; Berendse Henk W; Berg Daniela; Bhatia Kailash; de Bie Rob M A; Biffi Alessandro; Bloem Bas; Bochdanovits Zoltan; Bonin Michael; Brockmann Kathrin; Brooks Janet

来源：PLoS Genetics, 2011, 7(6): e1002142.

DOI：10.1371/journal.pgen.1002142

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<5x10(-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.

• 出版日期2011-6
• 单位河南工业大学