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Record W2134117922 · doi:10.1093/hmg/ddu552

[no title]

2015· article· en· W2134117922 on OpenAlexfundno aff
Tracy A. O’Mara, Jyotsna Batra, Timothy Cheng, Felicity Lose, Joe Dennis, Kyriaki Michailidou, Jonathan P. Tyrer, Shahana Ahmed, Kaltin Ferguson, Catherine S. Healey, Susanne Kaufmann, Kristine M. Hillman, Carina Walpole, Leire Moya, Pamela M. Pollock, Angela Jones, Kimberley Howarth, Lynn Martin, Maggie Gorman, Shirley Hodgson, Ma. Magdalena Echeverry de Polanco, Mónica Sans, Ángel Carracedo, Sergi Castellvı́-Bel, Augusto Rojas‐Martínez, Érika Maria Monteiro Santos, Manuel R. Teixeira, Luis G. Carvajal‐Carmona, Xiao‐Ou Shu, Jirong Long, Wei Zheng, Yong‐Bing Xiang, Grant W. Montgomery, Penelope M. Webb, Rodney J. Scott, Mark McEvoy, John Attia, Elizabeth Holliday, Nicholas G. Martin, Dale R. Nyholt, Anjali K. Henders, Peter A. Fasching, Alexander Hein, Matthias W. Beckmann, Stefan P. Renner, Thilo Dörk, Peter Hillemanns, Matthias Dürst

Bibliographic record

VenueMonash University Research Portal (Monash University) · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA modifications and cancer
Canadian institutionsnot available
FundersNational Cancer InstituteCanadian Institutes of Health ResearchFrancis Crick InstituteCancer Research UKWellcome Trust
KeywordsHNF1BSingle-nucleotide polymorphismEndometrial cancerLocus (genetics)BiologyGeneticsLinkage disequilibriumHaplotypeGenotypeAlleleSNPGenePromoterCancerGene expression

Abstract

fetched live from OpenAlex

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10−14, odds ratio = 0.86, 95% confidence interval = 0.82–0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.719
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.002
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0020.002
Research integrity0.0000.001
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 head0.079
GPT teacher head0.299
Teacher spread0.220 · 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.

Study designNot applicable
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

Citations58
Published2015
Admission routes1
Has abstractyes

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