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Author Notes:

E-mail: lbertram@molgen.mpg.de

See publication for full list of author contributions.

23andMe acknowledges Elizabeth Dorfman, Amy K. Kiefer, Emily M. Drabant, Uta Francke, Joanna L. Mountain, David Hinds, and Anne Wojcicki from 23andMe, as well as Samuel M. Goldman, Caroline M. Tanner, and J. William Langston from the Parkinson's Institute, Sunnyvale, CA, USA.

We also acknowledge the contribution of Mitsutoshi Yamamoto, Nobutaka Hattori, and Miho Murata for sample collection in the Japanese GWAS 1.0 [14].

We are grateful to the Alzheimer Research Forum—in particular to June Kinoshita, Colin Knep, Paula Noyes, and Gabrielle Ströbel—for hosting PDGene on their website.

We also thank the many PD researchers who have kindly provided us with genotype data and helpful information beyond those included in the original publications.

Finally, we would like to thank the many PD patients and control subjects who volunteered to participate in the individual studies.

See publication for full list of disclosures.

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.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Research 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).

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).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • GENETICS & HEREDITY
  • GENOME-WIDE ASSOCIATION
  • ALPHA-SYNUCLEIN
  • RISK-FACTORS
  • MUTATIONS
  • VARIANTS
  • SUSCEPTIBILITY
  • DATASETS
  • TRIALS
  • REGION
  • VPS35

Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database

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Journal Title:

PLoS Genetics

Volume:

Volume 8, Number 3

Publisher:

, Pages e1002548-e1002548

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Universal : Public Domain Dedication License (http://creativecommons.org/publicdomain/zero/1.0/).

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