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Record W3037991559 · doi:10.1101/2020.06.26.20141176

Association study of <i>DNAJC13, UCHL1, HTRA2, GIGYF2</i> and <i>EIF4G1</i> with Parkinson’s disease

2020· preprint· en· W3037991559 on OpenAlexafffund
Prabhjyot Saini, Uladzislau Rudakou, Eric Yu, Jennifer A. Ruskey, Farnaz Asayesh, Sandra B. Laurent, Dan Spiegelman, Stanley Fahn, Cheryl Waters, Oury Monchi, Yves Dauvilliers, Nicolas Dupré, Lior Greenbaum, Sharon Hassin‐Baer, Alberto J. Espay, Guy A. Rouleau, Roy N. Alcalay, Edward A. Fon, Ronald B. Postuma, Ziv Gan‐Or

Bibliographic record

VenuemedRxiv · 2020
Typepreprint
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsUniversity of CalgaryMcGill UniversityUniversité LavalMontreal Neurological Institute and Hospital
FundersNational Institutes of HealthCanada First Research Excellence FundCanadian Institutes of Health ResearchParkinson CanadaConsortium canadien en neurodégénérescence associée au vieillissementMcGill UniversityParkinson's FoundationBrookdale FoundationFonds de Recherche du Québec - SantéMichael J. Fox Foundation for Parkinson's Research
KeywordsGeneGeneticsParkinson's diseaseBiologyDiseaseAssociation testGenetic associationSingle-nucleotide polymorphismGenotypeMedicineInternal medicine

Abstract

fetched live from OpenAlex

Abstract Rare mutations in genes originally discovered in multi-generational families have been associated with increased risk of Parkinson’s Disease (PD). The involvement of rare variants in DNAJC13, UCHL1, HTRA2, GIGYF2 and EIF4G1 loci have been poorly studied or produced conflicting results across cohorts. However, they are still being often referred to as “PD-genes” and used in different models. To further elucidate the role of these five genes in PD, we fully sequenced them using molecular inversion probes in 2,408 PD patients and 3,444 controls from 3 different cohorts. A total of 788 rare variants were identified across the five genes and three cohorts. Burden analyses and optimized sequence Kernel association tests revealed no significant association between any of the genes and PD after correction for multiple comparisons. Our results do not support an association of the five tested genes with PD. Combined with previous studies, it is unlikely that any of these genes plays an important role in PD. Their designation as “ PARK ” genes should be reconsidered.

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)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.021
GPT teacher head0.260
Teacher spread0.239 · 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 designObservational
Domainnot available
GenreEmpirical

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

Citations2
Published2020
Admission routes2
Has abstractyes

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Same venuemedRxiv→Same topicParkinson's Disease Mechanisms and Treatments→French-language works237,207→