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Record W4214657318 · doi:10.1101/2022.02.18.22269402

Assessment of private variants in <i>PRKN, PARK7</i> and <i>PINK1</i> in Parkinson’s disease

2022· preprint· en· W4214657318 on OpenAlexaff
Jing Hu, Cheryl Waters, Dan Spiegelman, Edward A. Fon, Eric Yu, Farnaz Asayesh, Lynne Krohn, Prabhjyot Saini, Roy N. Alcalay, Sharon Hassin‐Baer, Ziv Gan‐Or, Dimitri Krainc, BaoRong Zhang, Bernabé I. Bustos, Steven Lubbe

Bibliographic record

VenuemedRxiv · 2022
Typepreprint
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
Fundersnot available
KeywordsAllelePINK1Minor allele frequencyDiseaseGeneticsParkinson's diseaseAllele frequencyGeneMedicineBiologyInternal medicine

Abstract

fetched live from OpenAlex

Abstract Recessive mutations in PRKN, PARK7 and PINK1 are established causes of early-onset Parkinson’s disease (EOPD). Previous studies have interrogated the role of heterozygous variants in these genes but mainly focused on rare (minor allele frequency [MAF] <1%) damaging variants or established mutations. Here, we assessed heterozygous private PRKN, PARK7 and PINK1 variants in PD risk in four large-scale PD case-control datasets by performing gene-wise burden analyses using sequencing data totaling 5,829 PD cases and 7,221 controls, and summary allele counts from 9,501 PD cases and 48,207 controls. Results showed no significant burden in all three genes after meta-analyses. Burden in EOPD (age at onset <50 years) and late-onset PD (≥50 years) remained nonsignificant. In summary, we found no evidence to support the association of the excess burden of heterozygous private variants in PRKN, PARK7 , and PINK1 with PD risk in the European population. Larger, more diverse cohorts are needed to accurately determine their role in PD.

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)0.007
metaresearch head score (Gemma)0.009
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 score0.007
Threshold uncertainty score0.035

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0070.009
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.003
Bibliometrics0.0010.002
Science and technology studies0.0000.001
Scholarly communication0.0020.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.297
Teacher spread0.277 · 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

Citations0
Published2022
Admission routes1
Has abstractyes

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