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- Title
Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database.
- Authors
M. Lill, Christina; Roehr, Johannes T.; McQueen, Matthew B.; Kavvoura, Fotini K.; Bagade, Sachin; Schjeide, Brit-Maren M.; Schjeide, Leif M.; Meissner, Esther; Zauft, Ute; Allen, Nicole C.; Liu, Tian; Schilling, Marcel; Anderson, Kari J.; Beecham, Gary; Berg, Daniela; Biernacka, Joanna M.; Brice, Alexis; DeStefano, Anita L.; Do, Chuong B.; Eriksson, Nicholas
- 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 performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls.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<5x10-8) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3,P A R K 1 6 , SNCA, STK39,a n d SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P=1.3x10-8). 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.
- Subjects
PARKINSON'S disease; GENOMES; GENETICS; GENOMICS; GENETIC polymorphisms
- Publication
PLoS Genetics, 2012, Vol 8, Issue 3, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1002548