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Record W2149345837 · doi:10.1002/ana.21063

A second major histocompatibility complex susceptibility locus for multiple sclerosis

2007· article· en· W2149345837 on OpenAlexaff
Tai Wai Yeo, Philip L. De Jager, Simon G. Gregory, Lisa F. Barcellos, Amie Walton, An Goris, Chiara Fenoglio, Maria Ban, Craig J. Taylor, Reyna S. Goodman, Emily Walsh, Cara S. Wolfish, Roger W. Horton, James A. Traherne, Stephan Beck, John Trowsdale, Stacy J. Caillier, Adrian J. Ivinson, Todd J. Green, Susan Pobywajlo, Eric S. Lander, Margaret A. Pericak‐Vance, Jonathan L. Haines, Mark J. Daly, Jorge R. Oksenberg, Stephen L. Hauser, Alastair Compston, David A. Hafler, John D. Rioux, Stephen Sawcer

Bibliographic record

VenueAnnals of Neurology · 2007
Typearticle
Languageen
FieldMedicine
TopicMultiple Sclerosis Research Studies
Canadian institutionsUniversité de MontréalMontreal Heart Institute
FundersNational Institutes of HealthVlaamse regeringFonds Wetenschappelijk OnderzoekWellcome TrustMultiple Sclerosis SocietyCambridge Philosophical SocietyCambridge Commonwealth TrustGlaxoSmithKlineNational Institute of Neurological Disorders and StrokeMedical Research CouncilCancer Research Institute
KeywordsGeneticsHuman leukocyte antigenLinkage disequilibriumLocus (genetics)Major histocompatibility complexAlleleBiologyGenotypingMultiple sclerosisHaplotypeGeneSingle-nucleotide polymorphismMicrosatelliteImmunologyGenotypeAntigen

Abstract

fetched live from OpenAlex

OBJECTIVE: Variation in the major histocompatibility complex (MHC) on chromosome 6p21 is known to influence susceptibility to multiple sclerosis with the strongest effect originating from the HLA-DRB1 gene in the class II region. The possibility that other genes in the MHC independently influence susceptibility to multiple sclerosis has been suggested but remains unconfirmed. METHODS: Using a combination of microsatellite, single nucleotide polymorphism, and human leukocyte antigen (HLA) typing, we screened the MHC in trio families looking for evidence of residual association above and beyond that attributable to the established DRB1*1501 risk haplotype. We then refined this analysis by extending the genotyping of classical HLA loci into independent cases and control subjects. RESULTS: Screening confirmed the presence of residual association and suggested that this was maximal in the region of the HLA-C gene. Extending analysis of the classical loci confirmed that this residual association is partly due to allelic heterogeneity at the HLA-DRB1 locus, but also reflects an independent effect from the HLA-C gene. Specifically, the HLA-C*05 allele, or a variant in tight linkage disequilibrium with it, appears to exert a protective effect (p = 3.3 x 10(-5)). INTERPRETATION: Variation in the HLA-C gene influences susceptibility to multiple sclerosis independently of any effect attributable to the nearby HLA-DRB1 gene.

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)0.002
metaresearch head score (Gemma)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.566
Threshold uncertainty score0.838

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
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 head0.302
GPT teacher head0.402
Teacher spread0.101 · 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

Citations175
Published2007
Admission routes1
Has abstractyes

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