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<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.
