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Record W3199562573 · doi:10.1038/s41531-021-00231-5

Fine mapping of the HLA locus in Parkinson’s disease in Europeans

2021· article· en· W3199562573 on OpenAlexafffund
Eric Yu, Aditya Ambati, Maren Stolp Andersen, Lynne Krohn, Mehrdad A. Estiar, Prabhjyot Saini, Konstantin Senkevich, Yuri L. Sosero, Ashwin Ashok Kumar Sreelatha, Jennifer A. Ruskey, Farnaz Asayesh, Dan Spiegelman, Mathias Toft, Marte K. Viken, Manu Sharma, Cornelis Blauwendraat, Lasse Pihlstrøm, Emmanuel Mignot, Ziv Gan‐Or

Bibliographic record

Venuenpj Parkinson s Disease · 2021
Typearticle
Languageen
FieldImmunology and Microbiology
TopicT-cell and B-cell Immunology
Canadian institutionsMcGill UniversityMcGill Genome CentreMontreal Neurological Institute and Hospital
FundersFonds de Recherche du Québec - SantéAvid RadiopharmaceuticalsSanofi GenzymeGenentechH. Lundbeck A/SServierAllerganNational Institutes of HealthBristol-Myers SquibbConsortium canadien en neurodégénérescence associée au vieillissementCanada First Research Excellence FundParkinson CanadaVoyager TherapeuticsDenali TherapeuticsNeurocrine BiosciencesMcGill UniversityPfizerBiogenCelgeneVerily Life SciencesTeva Pharmaceutical IndustriesSanofiGlaxoSmithKlineEli Lilly and CompanyMichael J. Fox Foundation for Parkinson's Research
KeywordsHuman leukocyte antigenLocus (genetics)Parkinson's diseaseDiseaseHaplotypeGeneticsGenetic associationAlleleBiologyImmunologyMedicineAntigenInternal medicineSingle-nucleotide polymorphismGenotypeGene

Abstract

fetched live from OpenAlex

Abstract We fine mapped the leukocyte antigen ( HLA) region in 13,770 Parkinson’s disease (PD) patients, 20,214 proxy-cases, and 490,861 controls of European origin. Four HLA types were associated with PD after correction for multiple comparisons, HLA-DQA1 *03:01, HLA-DQB1 *03:02, HLA-DRB1 *04:01, and HLA-DRB1 *04:04. Haplotype analyses followed by amino acid analysis and conditional analyses suggested that the association is protective and primarily driven by three specific amino acid polymorphisms present in most HLA-DRB1 *04 subtypes—11V, 13H, and 33H (OR = 0.87, 95% CI: 0.83–0.90, p < 8.23 × 10 −9 for all three variants). No other effects were present after adjustment for these amino acids. Our results suggest that specific HLA-DRB1 variants are associated with reduced risk of PD, providing additional evidence for the role of the immune system in PD. Although effect size is small and has no diagnostic significance, understanding the mechanism underlying this association may lead to the identification of new targets for therapeutics development.

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 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 score0.385
Threshold uncertainty score0.984

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.014
GPT teacher head0.218
Teacher spread0.204 · 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 teacher head, 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

Citations73
Published2021
Admission routes2
Has abstractyes

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