Genome-Wide Association Study Meta-Analysis for Parkinson Disease Motor Subtypes
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.
Full frame distilled prediction
Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
- Candidate categories
- none
- Consensus categories
- none
- Domain
- Candidate signal: noneConsensus signal: none
- Study design
- Candidate signal: ObservationalConsensus signal: Observational
- Genre
- Candidate signal: EmpiricalConsensus signal: Empirical
- Teacher disagreement score
- 0.127
- Threshold uncertainty score
- 0.540
- Validation status
machine_predicted_unvalidated·codex-gemma-dda1882f352a
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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.
- Teacher spread
- 0.244 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
<h3>Objective</h3> To discover genetic determinants of Parkinson disease (PD) motor subtypes, including tremor dominant (TD) and postural instability/gait difficulty (PIGD) forms. <h3>Methods</h3> In 3,212 PD cases of European ancestry, we performed a genome-wide association study (GWAS) examining 2 complementary outcome traits derived from the Unified Parkinson9s Disease Rating Scale, including dichotomous motor subtype (TD vs PIGD) or a continuous tremor/PIGD score ratio. Logistic or linear regression models were adjusted for sex, age at onset, disease duration, and 5 ancestry principal components, followed by meta-analysis. <h3>Results</h3> Among 71 established PD risk variants, we detected multiple suggestive associations with PD motor subtype, including <i>GPNMB</i> (<i>rs199351</i>, <i>p</i><sub>subtype</sub> = 0.01, <i>p</i><sub>ratio</sub> = 0.03), <i>SH3GL2</i> (<i>rs10756907</i>, <i>p</i><sub>subtype</sub> = 0.02, <i>p</i><sub>ratio</sub> = 0.01), <i>HIP1R</i> (<i>rs10847864</i>, <i>p</i><sub>subtype</sub> = 0.02), <i>RIT2</i> (<i>rs12456492</i>, <i>p</i><sub>subtype</sub> = 0.02), and <i>FBRSL1</i> (<i>rs11610045</i>, <i>p</i><sub>subtype</sub> = 0.02). A PD genetic risk score integrating all 71 PD risk variants was also associated with subtype ratio (<i>p</i> = 0.026, ß = −0.04, 95% confidence interval = −0.07–0). Based on top results of our GWAS, we identify a novel suggestive association at the <i>STK32B</i> locus (rs2301857, <i>p</i><sub>ratio</sub> = 6.6 × 10<sup>−7</sup>), which harbors an independent risk allele for essential tremor. <h3>Conclusions</h3> Multiple PD risk alleles may also modify clinical manifestations to influence PD motor subtype. The discovery of a novel variant at <i>STK32B</i> suggests a possible overlap between genetic risk for essential tremor and tremor-dominant 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.
The record
- Venue
- Neurology Genetics
- Topic
- Neurological disorders and treatments
- Field
- Medicine
- Canadian institutions
- not available
- Funders
- Institute of GeneticsNational Institute of Environmental Health SciencesNational Institute of Neurological Disorders and StrokeMedical Research CouncilNational Institutes of HealthAssistance publique-Hôpitaux de ParisFondation de FranceNational Cancer InstituteLandspítali HáskólasjúkrahúsBundesministerium für Bildung und ForschungUniversity of GlasgowParkinson's UKNational Institute on AgingNational Institute for Health and Care ResearchMultiple System Atrophy CoalitionBiogenHuffington FoundationAgence Nationale de la RechercheSol Goldman Charitable TrustCanada First Research Excellence FundAmerican Parkinson Disease AssociationConsortium canadien en neurodégénérescence associée au vieillissementDeutsche ForschungsgemeinschaftMcGill UniversityDemensförbundetCenter for Individualized Medicine, Mayo ClinicH. Lundbeck A/SBurroughs Wellcome FundLewy Body Dementia AssociationUniversity College LondonWellcome TrustUniversity of DundeeHelsingin YliopistoU.S. Department of DefenseItä-Suomen YliopistoLittle Family FoundationParkinson VerenigingMichael J. Fox Foundation for Parkinson's ResearchMayo ClinicU.S. Department of Health and Human ServicesHelsingin ja Uudenmaan SairaanhoitopiiriEU Joint Programme – Neurodegenerative Disease Research
- Keywords
- Genome-wide association studyConfidence intervalOdds ratioLogistic regressionInternal medicineDiseaseGenetic modelMeta-analysisMedicineGeneticsBiologyGenotypeSingle-nucleotide polymorphismGene
- Has abstract in OpenAlex
- yes