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Record W1557481987 · doi:10.1038/ncomms8146

Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1

2015· article· en· W1557481987 on OpenAlexafffund
Adrián Cortés, Sara L. Pulit, Paul Leo, Jenny J. Pointon, Philip C. Robinson, Michael H. Weisman, Michael M. Ward, Lianne S. Gensler, Xiaodong Zhou, Henri-Jean Garchon, Gilles Chiocchia, Johannes C. Nossent, Benedicte A. Lie, Øystein Førre, Jaakko Tuomilehto, Kari Laiho, Linda A. Bradbury, Dirk Elewaut, Rubén Burgos‐Vargas, Simon Stebbings, Louise Appleton, Claire Farrah, Jonathan C. Lau, Nigil Haroon, Juan Mulero, Francisco J. Blanco, Miguel Á. González‐Gay, Carlos López‐Larrea, Paul Bowness, Karl Gaffney, Hill Gaston, Dafna D. Gladman, Proton Rahman, Walter P. Maksymowych, J. Bart A. Crusius, Irene E. van der Horst‐Bruinsma, Raphael Valle-Oñate, Consuelo Romero‐Sánchez, Inger Myrnes Hansen, Fernando Pimentel‐Santos, Robert D. Inman, Javier Martı́n, Maxime Bréban, John D. Reveille, David M. Evans, Paul I. W. de Bakker, Matthew A. Brown

Bibliographic record

VenueNature Communications · 2015
Typearticle
Languageen
FieldMedicine
TopicSpondyloarthritis Studies and Treatments
Canadian institutionsUniversity of AlbertaMemorial University of NewfoundlandToronto Western HospitalUniversity of Toronto
FundersNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institute of Allergy and Infectious DiseasesVersus ArthritisMedical Research CouncilNational Institutes of HealthNational Institute for Health and Care ResearchArthritis SocietyAgence Nationale de la RechercheWellcome TrustNational Health and Medical Research CouncilEuropean CommissionArthritis Foundation
KeywordsAlleleSingle-nucleotide polymorphismGeneticsHaplotypeAnkylosing spondylitisHuman leukocyte antigenMajor histocompatibility complexSNPBiologyGenotypeHLA-BGenetic associationImmunologyEpistasisGeneAntigen

Abstract

fetched live from OpenAlex

Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.

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)0.002
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 score0.006
Threshold uncertainty score0.020

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
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)0.0060.000

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 head0.111
GPT teacher head0.352
Teacher spread0.242 · 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

Citations322
Published2015
Admission routes2
Has abstractyes

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