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Shared heritability and functional enrichment across six solid cancers
Xia Jiang, Hilary K. Finucane, Fredrick R. Schumacher, Stephanie L. Schmit, Jonathan P. Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline Kuchenbaecker, Joe Dennis, David V. Conti, Graham Casey, Mia M. Gaudet, Jeroen R. Huyghe, Demetrius Albanes, Melinda C. Aldrich, Angeline S. Andrew, Irene L. Andrulis, Hoda Anton‐Culver, Antonis C. Antoniou, Natalia Antonenkova, Susanne M. Arnold, Kristan J. Aronson, Banu Arun, Elisa V. Bandera, Rósa B. Barkardóttir, Daniel R. Barnes, Jyotsna Batra, Matthias W. Beckmann, Javier Benı́tez, Sara Benlloch, Andrew Berchuck, Sonja I. Berndt, Heike Bickeböller, Stephanie A. Bien, Carl Blomqvist, Stefania Boccia, Natalia Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, James D. Brenton, Mark N. Brook, Joan Brunet, Hans Brunnström, Daniel D. Buchanan, Barbara Burwinkel, Ralf Bützow, Gabriella Cadoni, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Peter T. 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Notice bibliographique
RevueNature Communications · 2019
Typearticle
Langueen
DomaineBiochemistry, Genetics and Molecular Biology
ThématiqueEpigenetics and DNA Methylation
Établissements canadiensUniversité LavalMemorial University of NewfoundlandUniversity of AlbertaSinai Health SystemUniversity of British ColumbiaMcGill UniversityCanada Research ChairsQueen's UniversityBC Cancer AgencyVancouver General HospitalPrincess Margaret Cancer CentreMount Sinai HospitalLunenfeld-Tanenbaum Research InstituteCentre hospitalier universitaire de QuébecRoyal Victoria HospitalUniversity Health NetworkUniversity of Toronto
Organismes subventionnairesDivision of Cancer Epidemiology and Genetics, National Cancer InstituteMedical Research and Materiel CommandNational Institute of Diabetes and Digestive and Kidney DiseasesFogarty International CenterNational Institute of General Medical SciencesNational Human Genome Research InstituteNational Institute on Drug AbuseNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteNational Institute on AgingServicio Gallego de SaludOntario Ministry of Research and InnovationNational Cancer InstituteEuropean Regional Development FundInstituto de Salud Carlos IIICancer Council NSWCancer Council VictoriaCanadian Cancer Society Research InstituteNorris Cotton Cancer CenterU.S. ArmyHellenic Health FoundationFreistaat SachsenBiomedical Research CouncilFederal Agency for Scientific OrganizationsPomorski Uniwersytet Medyczny W SzczecinieMutuelle Générale de l'Education NationaleInstitut Gustave-RoussyMinistero dello Sviluppo EconomicoUniversidad de OviedoCenter for Agroforestry, University of MissouriOulun YliopistoKWF KankerbestrijdingConseil Régional des Pays de la LoireVetenskapsrådetNational Medical Research CouncilNorges ForskningsrådStockholms Läns LandstingStavros Niarchos FoundationLigue Contre le CancerKuopion Yliopistollinen SairaalaAssociazione Italiana per la Ricerca sul CancroKarolinska InstitutetVanderbilt UniversityKorea Health Industry Development InstituteHungarian Scientific Research FundJapan Agency for Medical Research and DevelopmentDeutsche Gesetzliche UnfallversicherungHerlev HospitalNational Institute of Environmental Health SciencesSwedish Cancer FoundationMinistry of Health, Labour and WelfareUniversity of Southern CaliforniaCancerfondenAmerican Cancer SocietyRadboud UniversiteitCancer AustraliaRussian Foundation for Basic ResearchNational Health and Medical Research CouncilDeutsche KrebshilfeMinistry of Education, Science and TechnologyAcademia SinicaCalifornia Department of Public HealthNational Research Foundation of KoreaNational Natural Science Foundation of ChinaDepartament d'Universitats, Recerca i Societat de la InformacióInstitut National de la Santé et de la Recherche MédicaleProgramme Grants for Applied ResearchOvarian Cancer AustraliaRobert Bosch StiftungFisher Center for Alzheimer's Research FoundationProstate Cancer Foundation of AustraliaFundação de Amparo à Pesquisa do Estado de São PauloCanadian Institutes of Health ResearchEuropean CommissionMedizinischen Hochschule HannoverCancer Institute NSWUniversity College LondonAcademy of FinlandKing's College LondonLon V. Smith FoundationDeutscher Akademischer AustauschdienstHealth CanadaInstytut Medycyny Pracy im. prof. J. NoferaYayasan Sime DarbyNational Institute of Dental and Craniofacial ResearchUniversity of CambridgeNemzeti Kutatási Fejlesztési és Innovációs HivatalVirginia Department of HealthGovernment of CanadaGenome CanadaFred C. and Katherine B. Andersen FoundationGeorgia Clinical and Translational Science AllianceRoyal Marsden NHS Foundation TrustWellcome TrustJohns Hopkins UniversityOntario Institute for Cancer ResearchWorld Cancer Research FundBC Cancer FoundationCancer Care OntarioCancer Research SocietyInstitute of Biomedical Sciences, Academia SinicaDavid F. and Margaret T. Grohne Family FoundationCancer Prevention and Research Institute of TexasHelse VestAssociation Anne de Bretagne GenetiqueCancer Council South AustraliaMemorial Sloan-Kettering Cancer CenterCentre International de Recherche sur le CancerKreftforeningenSundhed og Sygdom, Det Frie ForskningsrådVanderbilt University Medical CenterDeutsches KrebsforschungszentrumPeter MacCallum FoundationFundación para el Fomento en Asturias de la Investigación Científica Aplicada y la TecnologíaHelsingin ja Uudenmaan SairaanhoitopiiriKræftens BekæmpelseDr. Ralph and Marian Falk Medical Research TrustRoswell Park Cancer InstituteCompagnia di San PaoloNational Institutes of HealthGroupement des Entreprises Françaises dans la lutte contre le CancerFlorida Department of HealthDivision of Cancer Prevention, National Cancer InstituteNational Breast Cancer FoundationEuropean Social FundMedical Research CouncilMayo Foundation for Medical Education and ResearchRutgers Cancer Institute of New JerseyJunta de Castilla y LeónSusan G. Komen for the CureTaiwan BiobankProstate Cancer FoundationOak FoundationNational Center for Research ResourcesAvon Foundation for WomenWorld Health OrganizationUniversity of South FloridaNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer ResearchNational Research FoundationCenters for Disease Control and PreventionNational Institute for Health and Care ResearchNational Cancer Research InstituteU.S. Department of Health and Human ServicesMinisterio de Economía y CompetitividadNational Center for Advancing Translational SciencesBundesministerium für Bildung und ForschungMinistry of Education, Culture, Sports, Science and TechnologyJapan Society for the Promotion of ScienceOvarian Cancer Research FundBreast Cancer CampaignGeorgetown UniversityCancer Council TasmaniaItä-Suomen YliopistoAgency for Science, Technology and ResearchState of Connecticut Department of Public HealthCancer Research InstituteOregon Health and Science UniversityCancer Research UKSheffield Hospitals CharityNordForskU.S. Department of DefenseUniversity of PittsburghBreast Cancer Research FoundationUniversity of Texas MD Anderson Cancer CenterPrincess Margaret Hospital FoundationMoffitt Cancer CenterMinnesota Ovarian Cancer AllianceFonds Wetenschappelijk OnderzoekRoy Castle Lung Cancer FoundationCalifornia Breast Cancer Research ProgramFondation du cancer du sein du Québec
Mots-clésHeritabilityComputational biologyBiologyGeneticsEvolutionary biology
Résumé
Abstract Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer ( r g = 0.57, p = 4.6 × 10 −8 ), breast and ovarian cancer ( r g = 0.24, p = 7 × 10 −5 ), breast and lung cancer ( r g = 0.18, p =1.5 × 10 −6 ) and breast and colorectal cancer ( r g = 0.15, p = 1.1 × 10 −4 ). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
score de la tête « metaresearch » (Codex)0,001
score de la tête « metaresearch » (Gemma)0,003
Version: metacan-v3-hybrid-931329e0061cStatut de validation: machine_predicted_unvalidated
Catégories candidatesaucune
Catégories consensuellesaucune
DomaineSignal candidat: aucune · Signal consensuel: aucune
Devis d'étudeSignal candidat: Observationnel · Signal consensuel: Observationnel
GenreSignal candidat: Empirique · Signal consensuel: Empirique
Score de désaccord entre enseignants0,003
Score d'incertitude au seuil0,008
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,002 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
Tête enseignante Opus0,016
Tête enseignante GPT0,321
Écart entre enseignants0,305 · la distance entre les deux têtes enseignantes sur ce seul travail
Statut de validation
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Les modèles n’ont appliqué aucune catégorie : rien dans la taxonomie ne correspondait à ce travail.
Devis d'étudeObservationnel
Domainenon disponible
GenreEmpirique
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».
En bref
Citations126
Publié2019
Routes d'admission2
Résumé présentoui