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Record W2944279315 · doi:10.1002/cpt.1493

Shared Genetic Risk Factors Across Carbamazepine‐Induced Hypersensitivity Reactions

2019· review· en· W2944279315 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.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueClinical Pharmacology & Therapeutics · 2019
Typereview
Languageen
FieldMedicine
TopicDrug-Induced Adverse Reactions
Canadian institutionsHealth Sciences CentreUniversity of TorontoSunnybrook Health Science Centre
FundersDaiichi Sankyo EuropeEuropean Regional Development FundNational Institute of Allergy and Infectious DiseasesMedical Research CouncilSvenska LäkaresällskapetNational Institutes of HealthPfizerVetenskapsrådetNational Institute of General Medical SciencesNational Institute for Health and Care ResearchUniversity of NottinghamNottingham University Hospitals NHS TrustAstraZenecaNational Institute of Diabetes and Digestive and Kidney DiseasesInstituto de Salud Carlos IIIAmgenWellcome TrustGlaxoSmithKline
KeywordsCarbamazepineHypersensitivity reactionDelayed hypersensitivityMedicinePharmacologyEpilepsyImmunologyPsychiatryAntigen

Abstract

fetched live from OpenAlex

Carbamazepine ( CBZ ) causes life‐threating T‐cell‐mediated hypersensitivity reactions, including serious cutaneous adverse reactions ( SCAR s) and drug‐induced liver injury ( CBZ ‐ DILI ). In order to evaluate shared or phenotype‐specific genetic predisposing factors for CBZ hypersensitivity reactions, we performed a meta‐analysis of two genomewide association studies ( GWAS ) on a total of 43 well‐phenotyped Northern and Southern European CBZ ‐ SCAR cases and 10,701 population controls and a GWAS on 12 CBZ ‐ DILI cases and 8,438 ethnically matched population controls. HLA ‐A*31:01 was identified as the strongest genetic predisposing factor for both CBZ ‐ SCAR (odds ratio ( OR ) = 8.0; 95% CI 4.10–15.80; P = 1.2 × 10 −9 ) and CBZ ‐ DILI ( OR = 7.3; 95% CI 2.47–23.67; P = 0.0004) in European populations. The association with HLA ‐A*31:01 in patients with SCAR was mainly driven by hypersensitivity syndrome ( OR = 12.9; P = 2.1 × 10 −9 ) rather than by Stevens‐Johnson syndrome/toxic epidermal necrolysis cases, which showed an association with HLA ‐B*57:01 . We also identified a novel risk locus mapping to ALK only for CBZ ‐ SCAR cases, which needs replication in additional cohorts and functional evaluation.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity, Insufficient payload (model declined to judge)
Consensus categoriesResearch integrity
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Other design · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.983
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0050.003
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0020.006
Insufficient payload (model declined to judge)0.0000.002

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 head0.357
GPT teacher head0.532
Teacher spread0.174 · 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