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Record W4362676794 · doi:10.1016/j.isci.2023.106590

Multi-trait genome-wide association study identifies a novel endometrial cancer risk locus that associates with testosterone levels

2023· article· en· W4362676794 on OpenAlexfundno aff
Xue Min Wang, Pik Fang Kho, Dhanya Ramachandran, Cemsel Bafligil, Frédéric Amant, Ellen L. Goode, Rodney J. Scott, Ian Tomlinson, D. Gareth Evans, Emma J. Crosbie, Thilo Dörk, Amanda B. Spurdle, Dylan M. Glubb, Tracy A. O’Mara

Bibliographic record

VenueiScience · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsnot available
FundersNational Cancer InstituteMedical Research CouncilCanadian Institutes of Health ResearchManchester Biomedical Research CentreOvarian Cancer Research FundNational Institutes of HealthCancer AustraliaNational Health and Medical Research CouncilCancer Research UKAustralian GovernmentQIMR Berghofer Medical Research InstituteWellcome TrustNational Institute for Health and Care ResearchGenome CanadaWilhelm Sander-Stiftung
KeywordsEndometrial cancerGenome-wide association studyMendelian randomizationOncologyBreast cancerBiologyCancerInternal medicineSingle-nucleotide polymorphismMedicineEndocrinologyGeneticsGenotypeGene

Abstract

fetched live from OpenAlex

To detect novel endometrial cancer risk variants, we leveraged information from endometrial cancer risk factors in a multi-trait GWAS analysis. We first assessed causal relationships between established and suspected endometrial cancer risk factors, and endometrial cancer using Mendelian randomization. Following multivariable analysis, five independent risk factors (waist circumference, testosterone levels, sex hormone binding globulin levels, age at menarche, and age at natural menopause) were included in a multi-trait Bayesian GWAS analysis. We identified three potentially novel loci that associate with endometrial cancer risk, one of which (7q22.1) replicated in an independent endometrial cancer GWAS dataset and was genome-wide significant in a meta-analysis. This locus may affect endometrial cancer risk through altered testosterone levels. Consistent with this, we observed colocalization between the signals for endometrial cancer risk and expression of CYP3A7 , a gene involved in testosterone metabolism. Thus, our findings suggest opportunities for hormone therapy to prevent or treat endometrial cancer.

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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.070
Threshold uncertainty score0.636

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.046
GPT teacher head0.307
Teacher spread0.261 · 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

Citations9
Published2023
Admission routes1
Has abstractyes

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