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Record W2796053515 · doi:10.1002/cam4.1445

Genetic overlap between endometriosis and endometrial cancer: evidence from cross‐disease genetic correlation and GWAS meta‐analyses

2018· review· en· W2796053515 on OpenAlexfundno aff
Jodie N. Painter, Tracy A. O’Mara, Andrew P. Morris, Timothy Cheng, Maggie Gorman, Lynn Martin, Shirley Hodson, Angela Jones, Nicholas G. Martin, Scott D. Gordon, Anjali K. Henders, John Attia, Mark McEvoy, Elizabeth Holliday, Rodney J. Scott, Penelope M. Webb, Peter A. Fasching, Matthias W. Beckmann, Arif B. Ekici, Alexander Hein, Matthias Rübner, Per Hall, Kamila Czene, Thilo Dörk, Matthias Dürst, Peter Hillemanns, Ingo B. Runnebaum, Frédéric Amant, Daniela Annibali, Jeroen Depreeuw, Adriaan Vanderstichele, Ellen L. Goode, Julie M. Cunningham, Sean C. Dowdy, Stacey J. Winham, Jone Trovik, Erling A. Høivik, Henrica M.J. Werner, Camilla Krakstad, Katie A. Ashton, Geoffrey Otton, Tony Proietto, Emma Tham, Miriam Mints, Shahana Ahmed, Catherine S. Healey, Mitul Shah, Paul D.P. Pharoah, Alison M. Dunning, Joe Dennis, Manjeet K. Bolla, Kyriaki Michailidou, Qin Wang, Jonathan P. Tyrer, John L. Hopper, Julian Peto, Anthony J. Swerdlow, Barbara Burwinkel, Hermann Brenner, Alfons Meindl, Hiltrud Brauch, Annika Lindblom, Jenny Chang‐Claude, Fergus J. Couch, Graham G. Giles, Vessela N. Kristensen, Angela Cox, Krina T. Zondervan, Dale R. Nyholt, Stuart MacGregor, Grant W. Montgomery, Ian Tomlinson, Douglas F. Easton, Deborah J. Thompson, Amanda B. Spurdle

Bibliographic record

VenueCancer Medicine · 2018
Typereview
Languageen
FieldMedicine
TopicEndometriosis Research and Treatment
Canadian institutionsnot available
FundersMedical Research and Materiel CommandNational Cancer InstituteCancer Council TasmaniaCancer Council QueenslandCancer Council VictoriaNational Health and Medical Research CouncilAustralian Research CouncilMedical Research CouncilNational Institutes of HealthPeter MacCallum FoundationVincent Fairfax Family FoundationHaukeland UniversitetssjukehusNorges ForskningsrådUniversitetet i BergenQIMR Berghofer Medical Research InstituteStockholms Läns LandstingKarolinska InstitutetAgency for Science, Technology and ResearchCanadian Institutes of Health ResearchCancerfondenOvarian Cancer Research FundCancer AustraliaCancer Council South AustraliaHunter Medical Research InstituteNational Institute for Health and Care ResearchFred C. and Katherine B. Andersen FoundationHelse VestCancer Council NSWSusan G. Komen for the CureOvarian Cancer AustraliaCancer Research UKWellcome TrustBreast Cancer Research FoundationUniversity of CambridgeKreftforeningenMayo Foundation for Medical Education and ResearchWellcomeRoswell Park Cancer InstituteEuropean CommissionU.S. Department of Defense
KeywordsGenome-wide association studyEndometriosisConcordanceEndometrial cancerBiologySNPGenetic associationOncologyMeta-analysisDiseaseEpidemiologyGeneticsSingle-nucleotide polymorphismCancerMedicineInternal medicineGenotypeGene

Abstract

fetched live from OpenAlex

Abstract Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg = 0.23, P = 9.3 × 10−3), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10−3) and concordance in effect direction (P = 2.0 × 10−3) between the two diseases. Cross‐disease GWAS meta‐analysis highlighted 13 distinct loci associated at P ≤ 10−5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10−8, OR = 1.11, 95% CI = 1.07–1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross‐disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.005
metaresearch head score (Gemma)0.014
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.005
Threshold uncertainty score0.028

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0050.014
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0050.005
Bibliometrics0.0040.005
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.334
GPT teacher head0.512
Teacher spread0.177 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designMeta-analysis
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

Citations88
Published2018
Admission routes1
Has abstractyes

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