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Record W2898290174 · doi:10.1002/mds.27527

Genotype‐phenotype relations for the Parkinson's disease genes SNCA, LRRK2, VPS35: MDSGene systematic review

2018· review· en· W2898290174 on OpenAlexafffund
Joanne Trinh, Florentine M.J. Zeldenrust, Jana Huang, Meike Kasten, Susen Schaake, Sonja Petkovic, Harutyun Madoev, Anne Grünewald, Shahad Almuammar, Inke R. König, Christina M. Lill, Katja Lohmann, Christine Klein, Connie Marras

Bibliographic record

VenueMovement Disorders · 2018
Typereview
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsToronto Western HospitalUniversity of Toronto
FundersCanadian Institutes of Health ResearchDeutsche ForschungsgemeinschaftAlexander von Humboldt-StiftungHermann und Lilly Schilling-Stiftung für Medizinische ForschungUniversität zu LübeckJoachim Herz StiftungInternational Parkinson and Movement Disorder Society
KeywordsLRRK2GenotypeMutationPhenotypeDiseaseGeneticsParkinson's diseaseGenetic heterogeneityBiologyGene mutationHuman geneticsMedicineGeneInternal medicine

Abstract

fetched live from OpenAlex

This comprehensive MDSGene review is devoted to the three autosomal-dominant PD forms: PARK-SNCA, PARK-LRRK2, and PARK-VPS35. It follows MDSGene's standardized data extraction protocol, screened a total of 2,972 citations, and is based on fully curated phenotypic and genotypic data on 937 patients with dominantly inherited PD attributed to 44 different mutations in SNCA, LRRK2, or VPS35. All of these data are also available in an easily searchable online database (www.mdsgene.org), which additionally provides descriptive summary statistics on phenotypic and genetic data. Despite the high degree of missingness of phenotypic features and unsystematic reporting of genotype data in the original literature, the present review recapitulates many of the previously described findings including later onset of disease (median age at onset: ∼49 years) compared to recessive forms of PD of an overall excellent treatment response. Our systematic review validates previous reports showing that SNCA mutation carriers have a younger age at onset compared to LRRK2 and VPS35 (P < 0.001). SNCA mutation carriers often have additional psychiatric symptoms, and although not exclusive to only LRRK2 or VPS35 mutation carriers, LRRK2 mutation carriers have a typical form of PD, and, lastly, VPS35 mutation carriers have good response to l-dopa. © 2018 International Parkinson and Movement Disorder Society.

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)0.006
metaresearch head score (Gemma)0.034
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Systematic review · Consensus signal: Systematic review
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.017
Threshold uncertainty score0.032

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0060.034
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0050.005
Bibliometrics0.0170.018
Science and technology studies0.0000.001
Scholarly communication0.0020.002
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.001

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 head0.035
GPT teacher head0.315
Teacher spread0.280 · 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.

The models applied no category: nothing in the taxonomy fit this work.
Study designSystematic review
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

Citations196
Published2018
Admission routes2
Has abstractyes

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