Lill, CM;
Roehr, JT;
McQueen, MB;
Kavvoura, FK;
Bagade, S;
Schjeide, B-MM;
Schjeide, LM;
... WTCCC2; + view all
(2012)
Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database.
PLOS GENETICS
, 8
(3)
, Article e1002548. 10.1371/journal.pgen.1002548.
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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 Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls.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.
| Type: | Article |
|---|---|
| Title: | Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pgen.1002548 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pgen.1002548 |
| Language: | English |
| Additional information: | This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Funding: The main funding for this study was provided by the Michael J. Fox Foundation for Parkinson's Disease (MJFF) with additional financial support by the Cure Alzheimer's Fund (CAF), the National Alliance for Research on Schizophrenia and Depression (NARSAD), Prize4Life, and EMD Serono (all to L Bertram). CM Lill was supported by a fellowship from the Deutscher Akademischer Austauschdienst (DAAD) and Fidelity Biosciences Research Initiative (FBRI). L Bertram is also supported by the German Ministry for Education and Research (BMBF). JPA Ioannidis was supported through the Tufts Clinical and Translational Science Institute (Tufts CTSI) under funding from the National Institute of Health/National Center for Research Resources (UL1 RR025752). Points of view or opinions in this paper are those of the authors and do not necessarily represent the official position or policies of the Tufts CTSI. M Sharma was supported by the Michael J. Fox Foundation. The NeuroGenetics Research Consortium GWAS [15] was funded by the Edmond J. Safra Michael J. Fox Foundation Global Genetics Consortium Initiative and NIH R01 NS 036960. The work of the International Parkinson's Disease Genomics Consortium (IPDGC) was supported in part by the Intramural Research Programs of the National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services: project numbers Z01 AG000949-02 and Z01-ES101986. In addition the work of the IPDGC was supported by the U.S. Department of Defense, award number W81XWH-09-2-0128. Portions of the work of the IPDGC utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, Md. (http://biowulf.nih.gov). T Foroud received funds from the National Institutes of Health (R01CA141668 and R01NS37167). C Klein is the recipient of a career development award from the Volkswagen Foundation and from the Hermann and Lilly Schilling Foundation. DM Maraganore acknowledges active funding support from the National Institutes of Health (2R01 ES10751), Alnylam Pharmaceuticals, Medtronic, and NorthShore University Health System. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1353817 |
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