hide
Free keywords:
genome-wide association
alpha-synuclein
risk-factors
mutations
variants
susceptibility
datasets
trials
region
vps35
Abstract:
More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson’s disease (PD). To
facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects
and meta-analyzes all published studies in the field. A systematic literature screen of ,27,000 articles yielded 828 eligible articles
from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association
studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performedmeta-analyses on more
than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Metaanalyses
on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci
showed genome-wide significant (P,561028) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT,
MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant
association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P=1.361028). All meta-analysis results are freely available on a
dedicated online database (www.pdgene.org), which is cross-linked with a customized track on the UCSC Genome Browser. Our
study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include
the results of future large-scale genetics projects, including next-generation sequencing studies.
