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Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database.

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 Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls.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 < 5 × 10(-8)) 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? =? 1.3 × 10(-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.

SUBMITTER: Lill CM

PROVIDER: S-EPMC3305333 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database.

Lill Christina M CM Roehr Johannes T JT McQueen Matthew B MB Kavvoura Fotini K FK Bagade Sachin S Schjeide Brit-Maren M BM Schjeide Leif M LM Meissner Esther E Zauft Ute U Allen Nicole C NC Liu Tian T Schilling Marcel M Anderson Kari J KJ Beecham Gary G Berg Daniela D Biernacka Joanna M JM Brice Alexis A DeStefano Anita L AL Do Chuong B CB Eriksson Nicholas N Factor Stewart A SA Farrer Matthew J MJ Foroud Tatiana T Gasser Thomas T Hamza Taye T Hardy John A JA Heutink Peter P Hill-Burns Erin M EM Klein Christine C Latourelle Jeanne C JC Maraganore Demetrius M DM Martin Eden R ER Martinez Maria M Myers Richard H RH Nalls Michael A MA Pankratz Nathan N Payami Haydeh H Satake Wataru W Scott William K WK Sharma Manu M Singleton Andrew B AB Stefansson Kari K Toda Tatsushi T Tung Joyce Y JY Vance Jeffery J Wood Nick W NW Zabetian Cyrus P CP Young Peter P Tanzi Rudolph E RE Khoury Muin J MJ Zipp Frauke F Lehrach Hans H Ioannidis John P A JP Bertram Lars L

PLoS genetics 20120315 3

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 availab ...[more]

PMID: 22438815

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Project description:BACKGROUND:Although genetic studies have reported a number of loci associated with cutaneous melanoma (CM) risk, a comprehensive synopsis of genetic association studies published in the field and systematic meta-analysis for all eligible polymorphisms have not been reported. METHODS:We systematically annotated data from all genetic association studies published in the CM field (n = 145), including data from genome-wide association studies (GWAS), and performed random-effects meta-analyses across all eligible polymorphisms on the basis of four or more independent case-control datasets in the main analyses. Supplementary analyses of three available datasets derived from GWAS and GWAS-replication studies were also done. Nominally statistically significant associations between polymorphisms and CM were graded for the strength of epidemiological evidence on the basis of the Human Genome Epidemiology Network Venice criteria. All statistical tests were two-sided. RESULTS:Forty-two polymorphisms across 18 independent loci evaluated in four or more datasets including candidate gene studies and available GWAS data were subjected to meta-analysis. Eight loci were identified in the main meta-analyses as being associated with a risk of CM (P < .05) of which four loci showed a genome-wide statistically significant association (P < 1 × 10(-7)), including 16q24.3 (MC1R), 20q11.22 (MYH7B/PIGU/ASIP), 11q14.3 (TYR), and 5p13.2 (SLC45A2). Grading of the cumulative evidence by the Venice criteria suggested strong epidemiological credibility for all four loci with genome-wide statistical significance and one additional gene at 9p23 (TYRP1). In the supplementary meta-analyses, a locus at 9p21.3 (CDKN2A/MTAP) reached genome-wide statistical significance with CM and had strong epidemiological credibility. CONCLUSIONS:To the best of our knowledge, this is the first comprehensive field synopsis and systematic meta-analysis to identify genes associated with an increased susceptibility to CM.

Dataset Information

Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database.

Publications

Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database.

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