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Record W2980136449 · doi:10.1093/hmg/ddz228

Inherited variants at 3q13.33 and 3p24.1 are associated with risk of diffuse large B-cell lymphoma and implicate immune pathways

2019· article· en· W2980136449 on OpenAlexaff
Geffen Kleinstern, Huihuang Yan, Michelle A.T. Hildebrandt, Joseph Vijai, Sonja I. Berndt, Hervé Ghesquières, James McKay, Sophia Wang, Alexandra Nieters, Yuanqing Ye, Alain Monnereau, Angela Brooks‐Wilson, Qing Lan, Mads Melbye, Rebecca D. Jackson, Lauren R. Teras, Mark P. Purdue, Claire M. Vajdic, Roel Vermeulen, Graham G. Giles, Pier Luigi Cocco, Brenda M. Birmann, Peter Kraft, Demetrius Albanes, Anne Zeleniuch‐Jacquotte, Simon Crouch, Yawei Zhang, Vivekananda Sarangi, Yan W. Asmann, Kenneth Offit, Gilles Salles, Xifeng Wu, Karin E. Smedby, Christine F. Skibola, Susan L. Slager, Nathaniel Rothman, Stephen J. Chanock, James R. Cerhan

Bibliographic record

VenueHuman Molecular Genetics · 2019
Typearticle
Languageen
FieldMedicine
TopicLymphoma Diagnosis and Treatment
Canadian institutionsBC Cancer Agency
FundersNational Center for Advancing Translational SciencesNational Institutes of HealthNational Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteUniversity of Texas MD Anderson Cancer CenterMemorial Sloan-Kettering Cancer CenterWorld Health Organization
KeywordsGenome-wide association studyLinkage disequilibriumSingle-nucleotide polymorphismBiologyLocus (genetics)GeneticsDiffuse large B-cell lymphomaGenetic associationSNPMinor allele frequencyGenotypingAlleleGenotypeGene

Abstract

fetched live from OpenAlex

We previously identified five single nucleotide polymorphisms (SNPs) at four susceptibility loci for diffuse large B-cell lymphoma (DLBCL) in individuals of European ancestry through a large genome-wide association study (GWAS). To further elucidate genetic susceptibility to DLBCL, we sought to validate two loci at 3q13.33 and 3p24.1 that were suggestive in the original GWAS with additional genotyping. In the meta-analysis (5662 cases and 9237 controls) of the four original GWAS discovery scans and three replication studies, the 3q13.33 locus (rs9831894; minor allele frequency [MAF] = 0.40) was associated with DLBCL risk [odds ratio (OR) = 0.83, P = 3.62 × 10-13]. rs9831894 is in linkage disequilibrium (LD) with additional variants that are part of a super-enhancer that physically interacts with promoters of CD86 and ILDR1. In the meta-analysis (5510 cases and 12 817 controls) of the four GWAS discovery scans and four replication studies, the 3p24.1 locus (rs6773363; MAF = 0.45) was also associated with DLBCL risk (OR = 1.20, P = 2.31 × 10-12). This SNP is 29 426-bp upstream of the nearest gene EOMES and in LD with additional SNPs that are part of a highly lineage-specific and tumor-acquired super-enhancer that shows long-range interaction with AZI2 promoter. These loci provide additional evidence for the role of immune function in the etiology of DLBCL, the most common lymphoma subtype.

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 score0.187
Threshold uncertainty score0.836

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 head0.009
GPT teacher head0.210
Teacher spread0.202 · 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

Citations26
Published2019
Admission routes1
Has abstractyes

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