MétaCan
Menu
Back to cohort
Record W4400761068 · doi:10.1158/1055-9965.epi-24-0496

Nonadditive Effects of Common Genetic Variants Have a Negligent Contribution to Cancer Heritability

2024· article· en· W4400761068 on OpenAlexfundno aff
Austin Hammermeister Suger, Tabitha A. Harrison, Barbara Henning, Constance Turman, Peter Kraft, Sara Lindström

Bibliographic record

VenueCancer Epidemiology Biomarkers & Prevention · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsnot available
FundersNational Center for Advancing Translational SciencesNational Institute of Allergy and Infectious DiseasesNational Cancer InstituteNational Heart, Lung, and Blood InstituteStrategic Research CouncilDepartament d'Universitats, Recerca i Societat de la InformacióInstituto de Salud Carlos IIIOntario Ministry of Research and InnovationNational Health and Medical Research CouncilWorld Cancer Research FundMedical Research CouncilNational Human Genome Research InstituteCancer Council VictoriaSchool of Medicine, Vanderbilt UniversityNational Center for Research ResourcesNational Institute of General Medical SciencesChonnam National University Hwasun HospitalCenters for Disease Control and PreventionDOD Prostate Cancer Research ProgramHellenic Health FoundationTaysDeutsche KrebshilfeSwedish Cancer FoundationAgence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du TravailVetenskapsrådetStockholms Läns LandstingServicio Gallego de SaludInnovationsfondenNorris Cotton Cancer CenterBundesministerium für Bildung und ForschungMinisterio de Economía y CompetitividadCanadian Institutes of Health ResearchCancerfondenRoyal Marsden NHS Foundation TrustChonnam National UniversityAcademy of FinlandForskningsrådet för Arbetsliv och SocialvetenskapGentofte HospitalCanary FoundationNational Institute for Health and Care ResearchKarolinska InstitutetUniversity of CambridgeZonMwNational Institute of Environmental Health SciencesProstate Cancer CanadaNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer ResearchFondation de FranceNational Cancer Research InstituteMovember FoundationMemorial Sloan-Kettering Cancer CenterFred Hutchinson Cancer Research CenterVanderbilt University Medical CenterDeutsches KrebsforschungszentrumU.S. Department of DefenseCancer Research UKUniformed Services University of the Health SciencesAmerican Cancer SocietyAssociazione Italiana per la Ricerca sul CancroState of Connecticut Department of Public HealthVanderbilt UniversityNational Institutes of HealthMike and Josie Harper Cancer Research InstituteNational Institute on Minority Health and Health DisparitiesEuropean Commission
KeywordsHeritabilityDominance (genetics)BiologyGenetic associationGenome-wide association studyMissing heritability problemGenetic architectureAdditive genetic effectsGeneticsPhenotypeGenotypeGenetic variantsSingle-nucleotide polymorphismGene

Abstract

fetched live from OpenAlex

BACKGROUND: Contribution of dominance effects to cancer heritability is unknown. We leveraged existing genome-wide association data for seven cancers to estimate the contribution of dominance effects to the heritability of individual cancer types. METHODS: We estimated the proportion of phenotypic variation caused by dominance genetic effects using genome-wide association data for seven cancers (breast, colorectal, lung, melanoma, nonmelanoma skin, ovarian, and prostate) in a total of 166,772 cases and 284,824 controls. RESULTS: We observed no evidence of a meaningful contribution of dominance effects to cancer heritability. By contrast, additive effects ranged between 0.11 and 0.34. CONCLUSIONS: In line with studies of other human traits, the dominance effects of common genetic variants play a minimal role in cancer etiology. IMPACT: These results support the assumption of an additive inheritance model when conducting cancer association studies with common genetic variants.

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)0.004
metaresearch head score (Gemma)0.019
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.004
Threshold uncertainty score0.024

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.019
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0000.001
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 head0.017
GPT teacher head0.349
Teacher spread0.331 · 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 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

Citations0
Published2024
Admission routes1
Has abstractyes

Explore more

Same venueCancer Epidemiology Biomarkers & PreventionSame topicGenetic Associations and EpidemiologyFrench-language works237,207