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Record W2959335923 · doi:10.1212/nxg.0000000000000348

Genetic risk of Parkinson disease and progression:

2019· article· en· W2959335923 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
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.

Bibliographic record

VenueNeurology Genetics · 2019
Typearticle
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsnot available
FundersNational Center for Research ResourcesNational Human Genome Research InstituteNational Institute on AgingNIHR Cambridge Biomedical Research CentreHelse Sør-Øst RHFMedical Research CouncilParkinsonfondenAllerganNational Institutes of HealthVoyager TherapeuticsNational Institute for Health and Care ResearchAgence Nationale de Sécurité du Médicament et des Produits de SantéCentre National de la Recherche ScientifiqueEvelyn TrustIpsenFonds Wetenschappelijk OnderzoekAssociation France ParkinsonAssistance Publique - Hôpitaux de ParisInstitut National de la Santé et de la Recherche MédicaleBiogenAgence Nationale de la RechercheH. Lundbeck A/SRosetrees TrustParkinson's UKRadboud UniversiteitHersenstichtingVerily Life SciencesGlaxoSmithKlineBarts CharityJohns Hopkins UniversityAmarin CorporationMichael J. Fox Foundation for Parkinson's ResearchParkinson's FoundationKinetics FoundationWellcome TrustZonMwBritannia PharmaceuticalsWeston Brain InstituteNational Institute of Neurological Disorders and StrokeSunovionNorges ForskningsrådUniversity of VirginiaNational Parkinson FoundationEU Joint Programme – Neurodegenerative Disease ResearchPfizerUniversity of RochesterUniversity of PennsylvaniaBrown UniversityCHDI FoundationMassachusetts General HospitalSmart Family FoundationParkinson's Disease FoundationU.S. Department of DefenseOhio State UniversityHarvard NeuroDiscovery CenterParkinson VerenigingNasjonalforeningen for FolkehelsenUniversity of Michigan
KeywordsAlleleOdds ratioHazard ratioLRRK2GenotypeInternal medicineDiseaseGeneticsMedicineBiologyParkinson's diseaseConfidence intervalGene

Abstract

fetched live from OpenAlex

<h3>Objective</h3> To determine if any association between previously identified alleles that confer risk for Parkinson disease and variables measuring disease progression. <h3>Methods</h3> We evaluated the association between 31 risk variants and variables measuring disease progression. A total of 23,423 visits by 4,307 patients of European ancestry from 13 longitudinal cohorts in Europe, North America, and Australia were analyzed. <h3>Results</h3> We confirmed the importance of <i>GBA</i> on phenotypes. <i>GBA</i> variants were associated with the development of daytime sleepiness (p.N370S: hazard ratio [HR] 3.28 [1.69–6.34]) and possible REM sleep behavior (p.T408M: odds ratio 6.48 [2.04–20.60]). We also replicated previously reported associations of <i>GBA</i> variants with motor/cognitive declines. The other genotype-phenotype associations include an intergenic variant near <i>LRRK2</i> and the faster development of motor symptom (Hoehn and Yahr scale 3.0 HR 1.33 [1.16–1.52] for the C allele of rs76904798) and an intronic variant in <i>PMVK</i> and the development of wearing-off effects (HR 1.66 [1.19–2.31] for the C allele of rs114138760). Age at onset was associated with <i>TMEM175</i> variant p.M393T (−0.72 [−1.21 to −0.23] in years), the C allele of rs199347 (intronic region of <i>GPNMB</i>, 0.70 [0.27–1.14]), and G allele of rs1106180 (intronic region of <i>CCDC62</i>, 0.62 [0.21–1.03]). <h3>Conclusions</h3> This study provides evidence that alleles associated with Parkinson disease risk, in particular <i>GBA</i> variants, also contribute to the heterogeneity of multiple motor and nonmotor aspects. Accounting for genetic variability will be a useful factor in understanding disease course and in minimizing heterogeneity in clinical trials.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.016
Threshold uncertainty score0.435

Codex and Gemma teacher scores by category

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

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 head0.010
GPT teacher head0.258
Teacher spread0.249 · 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