Shared heritability and functional enrichment across six solid cancers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Xia Jiang, Hilary K. Finucane, Fredrick R. Schumacher, Stephanie L. Schmit, Jonathan P. Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B. 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 N. Antonenkova, Susanne M. Arnold, Kristan J. Aronson, Banu K. Arun, Elisa V. Bandera, Rosa B. Barkardottir, Daniel R. Barnes, Jyotsna Batra, Matthias W. Beckmann, Javier Benitez, Sara Benlloch, Andrew Berchuck, Sonja I. Berndt, Heike Bickeböller, Stephanie A. Bien, Carl Blomqvist, Stefania Boccia, Natalia V. 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 Butzow, Gabriella Cadoni, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Peter T. Campbell, Géraldine Cancel-Tassin, Lisa Cannon-Albright, Daniele Campa, Neil Caporaso, André L. Carvalho, Andrew T. Chan, Jenny Chang-Claude, Stephen J. Chanock, Chu Chen, David C. Christiani, Kathleen B. M. Claes, Frank Claessens, Judith 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 Diez, Manuela Gago-Dominguez, Jenny L. Donovan, Thilo Dörk, Eric J. Duell, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, 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 J. Gallinger, Patricia A. Ganz, Judy Garber, José A. García-Sáenz, Simon A. Gayther, Graham G. Giles, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Ellen L. Goode, Marc T. Goodman, Gary Goodman, Kjell Grankvist, Mark H. Greene, Henrik Gronberg, 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 Houlston, Peter J. Hulick, David J. Hunter, David G. Huntsman, Gregory Idos, Evgeny N. Imyanitov, Sue Ann Ingles, Claudine Isaacs, Anna Jakubowska, Paul 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, Elza Khusnutdinova, Adam S. Kibel, Lambertus A. Kiemeney, Jeri Kim, Susanne K. Kjaer, Julia A. Knight, Manolis Kogevinas, Zsofia Kote-Jarai, Stella Koutros, Vessela N. Kristensen, Jolanta Kupryjanczyk, 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 Maehle, Christiane Maier, Arto Mannermaa, Loic Le Marchand, Sara Margolin, Taymaa May, Lesley McGuffog, Alfons Meindl, Pooja Middha, Austin Miller, Roger L. Milne, Robert J. MacInnis, Francesmary Modugno, Marco Montagna, Victor Moreno, Kirsten B. Moysich, Lorelei Mucci, Kenneth Muir, Anna Marie Mulligan, Katherine L. Nathanson, David E. Neal, Andrew R. Ness, Susan L. Neuhausen, Heli Nevanlinna, Polly A. Newcomb, Lisa F. Newcomb, Finn Cilius Nielsen, Liene Nikitina-Zake, Børge G. Nordestgaard, Robert L. Nussbaum, Kenneth Offit, Edith Olah, Ali Amin Al Olama, Olufunmilayo I. Olopade, Andrew F. Olshan, Håkan Olsson, Ana Osorio, Hardev Pandha, Jong Y. Park, Nora Pashayan, Michael T. Parsons, Tanja Pejovic, Kathryn L. Penney, Wilbert H M. Peters, Catherine M. Phelan, Amanda I. Phipps, Dijana Plaseska-Karanfilska, Miranda Pring, Darya Prokofyeva, Paolo Radice, Kari Stefansson, 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, V. Wendy Setiawan, Hongbing Shen, Erin M. Siegel, Weiva Sieh, Christian F. Singer, Martha L. Slattery, Karina Dalsgaard Sorensen, Melissa C. Southey, Amanda B. Spurdle, Janet L. Stanford, Victoria L. Stevens, Sebastian Stintzing, Jennifer Stone, Karin Sundfeldt, Rebecca Sutphen, Anthony J. Swerdlow, Eloiza H. Tajara, Catherine M. Tangen, Adonina Tardon, 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 Elías Aguado-Barrera, Qin Wang, Penelope M. Webb, Clarice R. Weinberg, Stephanie Weinstein, Mark C. Weissler, Jeffrey N. Weitzel, Catharine M. L. West, Emily White, Alice S. Whittemore, H-Erich Wichmann, Fredrik Wiklund, Robert Winqvist, Alicja Wolk, Penella Woll, Michael Woods, Anna H. Wu, Xifeng Wu, Drakoulis Yannoukakos, Wei Zheng, Shanbeh Zienolddiny, Argyrios Ziogas, Kristin K. Zorn, Jacqueline M. Lane, Richa Saxena, Duncan Thomas, Rayjean J. Hung, Brenda Diergaarde, James McKay, Ulrike Peters, Li Hsu, Montserrat García-Closas, Rosalind A. Eeles, Georgia Chenevix-Trench, Paul J. Brennan, Christopher A. Haiman, Jacques Simard, Douglas F. Easton, Stephen B. Gruber, Paul D. P. Pharoah, Alkes L. Price, Bogdan Pasaniuc, Christopher I. Amos, Peter Kraft, Sara Lindström

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 (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 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. More... »

PAGES

431

References to SciGraph publications

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    10

    Author Affiliations

  • Karolinska Institute
  • Broad Institute
  • University Hospitals of Cleveland
  • Moffitt Cancer Center
  • University of Cambridge
  • Dartmouth College
  • Cyprus Institute of Neurology and Genetics
  • International Agency For Research On Cancer
  • University College London
  • University of Virginia
  • American Cancer Society
  • Fred Hutchinson Cancer Research Center
  • National Cancer Institute
  • Vanderbilt University Medical Center
  • Dartmouth–Hitchcock Medical Center
  • University of Toronto
  • University of California, Irvine
  • University of Kentucky
  • Queen's University
  • The University of Texas MD Anderson Cancer Center
  • Rutgers University
  • University of Iceland
  • Queensland University of Technology
  • Centre for Biomedical Network Research on Rare Diseases
  • Institute of Cancer Research
  • Duke University Hospital
  • Universitätsmedizin Göttingen
  • University of Washington
  • Örebro University Hospital
  • Catholic University of the Sacred Heart
  • Hannover Medical School
  • University of Copenhagen
  • German Cancer Research Center
  • Cancer Research UK Cambridge Institute
  • Institut Català d'Oncologia
  • Lund University
  • Royal Melbourne Hospital
  • Hospital Clínico San Carlos
  • University of Melbourne
  • Tenon Hospital
  • George E. Wahlen Department of VA Medical Center
  • University of Pisa
  • Hospital de Câncer de Barretos
  • Massachusetts General Hospital
  • University Cancer Center Hamburg
  • Harvard University
  • Ghent University
  • KU Leuven
  • Erasmus University Medical Center
  • University of Puerto Rico, Medical Sciences Campus
  • Mayo Clinic
  • University of Sheffield
  • Pomeranian Medical University
  • Temple University Health System
  • Westmead Hospital
  • Leiden University Medical Center
  • Hospital Universitari Vall d'Hebron
  • University of California, San Diego
  • University of Bristol
  • University of Westminster
  • University of Southampton
  • University of Southern California
  • University of Manchester
  • University of California Los Angeles
  • University of Pittsburgh
  • University of Liverpool
  • National Centre of Scientific Research Demokritos
  • Tel Aviv University
  • Toronto General Hospital
  • Dana–Farber Cancer Institute
  • Cedars-Sinai Medical Center
  • Monash University
  • University of Kansas Medical Center
  • McGill University
  • University of Utah
  • Swedish Medical Center
  • Umeå University
  • University of Paris-Sud
  • Stockholm South General Hospital
  • Princess Margaret Cancer Centre
  • National Institute of Occupational Health
  • Herlev Hospital
  • Seoul National University
  • University of Chicago
  • University of British Columbia
  • Georgetown University
  • Peter MacCallum Cancer Centre
  • Stanford University
  • Medical University of Sofia
  • Medical University of South Carolina
  • Institute of Biochemistry and Genetics of Ufa Scientific Centre
  • Brigham and Women's Hospital
  • Radboud University Nijmegen Medical Centre
  • Danish Cancer Society
  • Pompeu Fabra University
  • National Institutes of Health
  • Oslo University Hospital
  • Centrum Onkologii Instytut
  • Maastricht University Medical Centre
  • BC Cancer Agency
  • Washington State University
  • Carmel Medical Center
  • University Medical Center Hamburg-Eppendorf
  • New York University Langone Medical Center
  • Servicio Gallego de Salud
  • Mayo Clinic
  • Istituto Oncologico Veneto
  • University Hospital Ulm
  • Kuopio University Hospital
  • University of Hawaii at Manoa
  • Technical University Munich
  • Heidelberg University
  • Roswell Park Cancer Institute
  • University of Warwick
  • University Health Network
  • City Of Hope National Medical Center
  • Latvian Biomedical Research and Study Centre
  • University of California, San Francisco
  • Memorial Sloan Kettering Cancer Center
  • National Institute of Oncology
  • University of North Carolina at Chapel Hill
  • University of Surrey
  • QIMR Berghofer Medical Research Institute
  • Oregon Health & Science University
  • Macedonian Academy of Sciences and Arts
  • Bashkir State University
  • deCODE Genetics (Iceland)
  • The Kinghorn Cancer Centre
  • University of Pretoria
  • Yale University
  • German Center for Lung Research
  • Icahn School of Medicine at Mount Sinai
  • University Hospital of Heraklion
  • National Institute of Environmental Health Sciences
  • King's College London
  • University of Tampere
  • Antoni van Leeuwenhoek Hospital
  • Nanjing Medical University
  • Medical University of Vienna
  • Aarhus University
  • University of Western Australia
  • University of Gothenburg
  • University of South Florida
  • University of Sao Paulo
  • University of Oviedo
  • University of Porto
  • Columbia University
  • Odense University Hospital
  • University of Bergen
  • The Ohio State University
  • Pontifical Xavierian University
  • University of Oxford
  • Beth Israel Deaconess Medical Center
  • University of Alberta
  • Universitaire Ziekenhuizen Leuven
  • Fundación Pública Galega de Medicina Xenómica
  • University of Oulu
  • Uppsala University
  • Memorial University of Newfoundland
  • University of Pittsburgh Cancer Institute
  • Centre Hospitalier Universitaire de Québec
  • Baylor College of Medicine
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-08054-4

    DOI

    http://dx.doi.org/10.1038/s41467-018-08054-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111664801

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30683880


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