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Record W2111957326 · doi:10.1371/journal.pgen.1002548

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

2012· review· en· W2111957326 on OpenAlexaff
Christina M. Lill, Johannes T. Roehr, Matthew B. McQueen, Fotini K. Kavvoura, Sachin Bagade, Brit‐Maren M. Schjeide, Leif M. Schjeide, Esther Meissner, Ute Zauft, Nicole C. Allen, Tian Liu, Marcel Schilling, Kari J. Anderson, Gary W. Beecham, Daniela Berg, Joanna M. Biernacka, Alexis Brice, Anita L. DeStefano, Nicholas Eriksson, Stewart A. Factor, Matthew J. Farrer, Tatiana Foroud, Thomas Gasser, Taye H. Hamza, John Hardy, Peter Heutink, Gully Burns, Christine Klein, Jeanne C. Latourelle, Demetrius M. Maraganore, Eden R. Martin, María Martínez, Richard H. Myers, Michael A. Nalls, Nathan Pankratz, Haydeh Payami, Wataru Satake, William K. Scott, Manu Sharma, Andrew Singleton, Kāri Stefánsson, Tatsushi Toda, Joyce Y. Tung, Jeffery M. Vance, Cyrus P. Zabetian, Peter Young, Rudolph E. Tanzi, Muin J. Khoury, Frauke Zipp, Hans Lehrach, John P. A. Ioannidis, Lars Bertram

Bibliographic record

VenuePLoS Genetics · 2012
Typereview
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsUniversity of British Columbia
FundersNational Center for Research ResourcesNational Institute of Environmental Health SciencesNational Cancer InstituteNational Institute on AgingFoundation for Biomedical Research and InnovationBundesministerium für Bildung und ForschungEisaiParkinson's UKEMD SeronoHermann und Lilly Schilling-Stiftung für Medizinische ForschungU.S. Department of DefenseEli Lilly and CompanyEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Alliance for Research on Schizophrenia and DepressionH. Lundbeck A/SFidelity BiosciencesNational Institute of Neurological Disorders and StrokePrize4LifeCure Alzheimer's FundU.S. Department of Health and Human ServicesDeutscher Akademischer AustauschdienstMayo Foundation for Medical Education and ResearchNational Institutes of HealthVolkswagen FoundationMichael J. Fox Foundation for Parkinson's ResearchNorthShore University HealthSystemMayo ClinicAlnylam Pharmaceuticals
KeywordsGenome-wide association studyMeta-analysisBiologyGenetic associationImputation (statistics)Single-nucleotide polymorphismGenetics1000 Genomes ProjectBioinformaticsComputational biologyGenotypeMedicineGeneMissing dataComputer scienceInternal medicine

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.015
metaresearch head score (Gemma)0.046
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (broad)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.992
Threshold uncertainty score0.080

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0150.046
Meta-epidemiology (narrow)0.0020.002
Meta-epidemiology (broad)0.0080.007
Bibliometrics0.0250.031
Science and technology studies0.0000.000
Scholarly communication0.0030.001
Open science0.0020.003
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0160.002

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.534
GPT teacher head0.468
Teacher spread0.066 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

Study designMeta-analysis
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations543
Published2012
Admission routes1
Has abstractyes

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