← Back to cohort
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. Campbell, Géraldine Cancel‐Tassin, Lisa Cannon‐Albright, Daniele Campa, Neil E. Caporaso, André Lopes Carvalho, Andrew T. Chan, Jenny Chang‐Claude, Stephen J. Chanock, Chu Chen, David C. Christiani, Kathleen Claes, Frank Claessens, Judith A. Clements, J. Margriet Collée, Marcia Cruz Correa, Fergus J. Couch, Angela Cox, Julie M. Cunningham, Cezary Cybulski, Kamila Czene, Mary B. Daly, Anna DeFazio, Peter Devilee, Orland Dı́ez, Manuela Gago-Domínguez, Jenny Donovan, Thilo Dörk, Eric J. Duell, Alison M. Dunning, Miriam Dwek, Christopher K. Edlund, Digna R. Velez Edwards, Carolina Ellberg, D. Gareth Evans, Peter A. Fasching, Robert L. Ferris, Triantafillos Liloglou, Jane C. Figueiredo, Olivia Fletcher, Renée T. Fortner, Florentia Fostira, Silvia Franceschi, Eitan Friedman, Steven Gallinger, Patricia A. Ganz, Judy E. Garber, José Á. García-Sáenz, Simon A. Gayther, Graham G. Giles, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Ellen L. Goode, Marc T. Goodman, Gary E. Goodman, Kjell Grankvist, Mark H. Greene, Henrik Grönberg, Jacek Gronwald, Pascal Guénel, Niclas Håkansson, Per Hall, Ute Hamann, Freddie C. Hamdy, Robert J. Hamilton, Jochen Hampe, Aage Haugen, Florian Heitz, Rolando Herrero, Peter Hillemanns, Michael Hoffmeister, Estrid Høgdall, Yun‐Chul Hong, John L. Hopper, Richard S. Houlston, Peter J. Hulick, David J. Hunter, David G. Huntsman, Gregory Idos, Evgeny N. Imyanitov, Sue A. Ingles, Claudine Isaacs, Anna Jakubowska, Paul A. James, Mark A. Jenkins, Mattias Johansson, Mikael Johansson, Esther M. John, Amit D. Joshi, Radka Kaneva, Beth Y. Karlan, Linda E. Kelemen, Tabea Kühl, Kay‐Tee Khaw, Э. К. Хуснутдинова, Adam S. Kibel, Lambertus A. Kiemeney, Jeri Kim, Susanne K. Kjær, Julia A. Knight, Manolis Kogevinas, Zsofia Kote‐Jarai, Stella Koutros, Vessela N. Kristensen, Jolanta Kupryjańczyk, Martin Lacko, Stephan Lam, Diether Lambrechts, Maria Teresa Landi, Philip Lazarus, Nhu D. Le, Eunjung Lee, Flavio Lejbkowicz, Heinz‐Josef Lenz, Goska Leslie, Davor Lessel, Jenny Lester, Douglas A. Levine, Li Li, Christopher I. Li, Annika Lindblom, Noralane M. Lindor, Geoffrey Liu, Fotios Loupakis, Jan Lubiński, Lovise Mæhle, Christiane Maier, Loı̈c Le Marchand, Sara Margolin, Taymaa May, Lesley McGuffog, Alfons Meindl, Pooja Middha, Austin Miller, Roger L. Milne, Robert J. MacInnis, Francesmary Modugno, Marco Montagna, Vı́ctor Moreno, Kirsten B. Moysich, Lorelei A. Mucci, Kenneth Muir, Anna Marie Mulligan, Katherine L. Nathanson, David E. Neal, Susan L. Neuhausen, Heli Nevanlinna, Polly A. Newcomb, Lisa F. Newcomb, Finn Cilius Nielsen, Liene Ņikitina-Zaķe, Børge G. Nordestgaard, Robert L. Nussbaum, Kenneth Offit, Edith Oláh, Ali Amin Al Olama, Olufunmilayo I. Olopade, Andrew F. Olshan, Håkan Olsson, Ana Osório, Hardev Pandha, Jong Y. Park, Nora Pashayan, Michael T. Parsons, Tanja Pejović, Kathryn L. Penney, Wilbert H.M. Peters, Catherine M. Phelan, Amanda I. Phipps, Dijana Plaseska‐Karanfilska, Miranda Pring, Darya Prokofyeva, Paolo Radice, Kāri Stefánsson, Susan J. Ramus, Leon Raskin, Gad Rennert, Hedy S. Rennert, Elizabeth J. van Rensburg, Marjorie J. Riggan, Harvey A. Risch, Angela Risch, Monique J. Roobol, Barry S. Rosenstein, Mary Anne Rossing, Kim De Ruyck, Emmanouil Saloustros, Dale P. Sandler, Elinor J. Sawyer, Matthew B. Schabath, Johanna Schleutker, Marjanka K. Schmidt, Veronica Wendy Setiawan, Hongbing Shen, Erin M. Siegel, Weiva Sieh, Christian F. Singer, Martha L. Slattery, Karina D. Sørensen, Melissa C. Southey, Amanda B. Spurdle, Janet L. Stanford, Victoria L. Stevens, Sebastian Stintzing, Jennifer Stone, Karin Sundfeldt, Rebecca Sutphen, Anthony J. Swerdlow, Eloíza H. Tajara, Catherine M. Tangen, Adonina Tardón, Jack A. Taylor, M. Dawn Teare, Manuel R. Teixeira, Mary Beth Terry, Kathryn L. Terry, Stephen N. Thibodeau, Mads Thomassen, Line Bjørge, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Paul A. Townsend, Ruth C. Travis, Nadine Tung, Shelley S. Tworoger, Cornelia M. Ulrich, Nawaid Usmani, Celine M. Vachon, Els Van Nieuwenhuysen, Ana Vega, Miguel E. Aguado‐Barrera, Qin Wang, Penelope M. Webb, Clarice R. Weinberg, Stephanie J. Weinstein, Mark C. Weissler, Jeffrey N. Weitzel, Catharine West, Emily White, Alice S. Whittemore, H‐Erich Wichmann, Fredrik Wiklund, Robert Winqvist, Alicja Wolk, Penella J. Woll, Michael O. Woods, Anna H. Wu, Xifeng Wu, Drakoulis Yannoukakos, Wei Zheng, Shanbeh Zienolddiny, Argyrios Ziogas, Kristin K. Zorn, Jacqueline M. Lane, Richa Saxena, Duncan C. Thomas, Brenda Diergaarde, James McKay, Ulrike Peters, Li Hsu, Montserrat García‐Closas, Rosalind A. Eeles, Georgia Chenevix‐Trench, Paul Brennan, Christopher A. Haiman, Jacques Simard, Douglas F. Easton, Stephen B. Gruber, Paul D.P. Pharoah, Alkes L. Price, Bogdan Paşaniuc, Christopher I. Amos, Peter Kraft, Sara Lindström
Bibliographic record
VenueNature Communications · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsUniversité 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
FundersDivision 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
KeywordsHeritabilityComputational biologyBiologyGeneticsEvolutionary biology
Abstract
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.
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 imitationNot 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)0.001
metaresearch head score (Gemma)0.003
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 score0.003
Threshold uncertainty score0.008
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
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 head0.016
GPT teacher head0.321
Teacher spread0.305 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine 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
Citations126
Published2019
Admission routes2
Has abstractyes