Discovery of common and rare genetic risk variants for colorectal cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-01

AUTHORS

Jeroen R. Huyghe, Stephanie A. Bien, Tabitha A. Harrison, Hyun Min Kang, Sai Chen, Stephanie L. Schmit, David V. Conti, Conghui Qu, Jihyoun Jeon, Christopher K. Edlund, Peyton Greenside, Michael Wainberg, Fredrick R. Schumacher, Joshua D. Smith, David M. Levine, Sarah C. Nelson, Nasa A. Sinnott-Armstrong, Demetrius Albanes, M. Henar Alonso, Kristin Anderson, Coral Arnau-Collell, Volker Arndt, Christina Bamia, Barbara L. Banbury, John A. Baron, Sonja I. Berndt, Stéphane Bézieau, D. Timothy Bishop, Juergen Boehm, Heiner Boeing, Hermann Brenner, Stefanie Brezina, Stephan Buch, Daniel D. Buchanan, Andrea Burnett-Hartman, Katja Butterbach, Bette J. Caan, Peter T. Campbell, Christopher S. Carlson, Sergi Castellví-Bel, Andrew T. Chan, Jenny Chang-Claude, Stephen J. Chanock, Maria-Dolores Chirlaque, Sang Hee Cho, Charles M. Connolly, Amanda J. Cross, Katarina Cuk, Keith R. Curtis, Albert de la Chapelle, Kimberly F. Doheny, David Duggan, Douglas F. Easton, Sjoerd G. Elias, Faye Elliott, Dallas R. English, Edith J. M. Feskens, Jane C. Figueiredo, Rocky Fischer, Liesel M. FitzGerald, David Forman, Manish Gala, Steven Gallinger, W. James Gauderman, Graham G. Giles, Elizabeth Gillanders, Jian Gong, Phyllis J. Goodman, William M. Grady, John S. Grove, Andrea Gsur, Marc J. Gunter, Robert W. Haile, Jochen Hampe, Heather Hampel, Sophia Harlid, Richard B. Hayes, Philipp Hofer, Michael Hoffmeister, John L. Hopper, Wan-Ling Hsu, Wen-Yi Huang, Thomas J. Hudson, David J. Hunter, Gemma Ibañez-Sanz, Gregory E. Idos, Roxann Ingersoll, Rebecca D. Jackson, Eric J. Jacobs, Mark A. Jenkins, Amit D. Joshi, Corinne E. Joshu, Temitope O. Keku, Timothy J. Key, Hyeong Rok Kim, Emiko Kobayashi, Laurence N. Kolonel, Charles Kooperberg, Tilman Kühn, Sébastien Küry, Sun-Seog Kweon, Susanna C. Larsson, Cecelia A. Laurie, Loic Le Marchand, Suzanne M. Leal, Soo Chin Lee, Flavio Lejbkowicz, Mathieu Lemire, Christopher I. Li, Li Li, Wolfgang Lieb, Yi Lin, Annika Lindblom, Noralane M. Lindor, Hua Ling, Tin L. Louie, Satu Männistö, Sanford D. Markowitz, Vicente Martín, Giovanna Masala, Caroline E. McNeil, Marilena Melas, Roger L. Milne, Lorena Moreno, Neil Murphy, Robin Myte, Alessio Naccarati, Polly A. Newcomb, Kenneth Offit, Shuji Ogino, N. Charlotte Onland-Moret, Barbara Pardini, Patrick S. Parfrey, Rachel Pearlman, Vittorio Perduca, Paul D. P. Pharoah, Mila Pinchev, Elizabeth A. Platz, Ross L. Prentice, Elizabeth Pugh, Leon Raskin, Gad Rennert, Hedy S. Rennert, Elio Riboli, Miguel Rodríguez-Barranco, Jane Romm, Lori C. Sakoda, Clemens Schafmayer, Robert E. Schoen, Daniela Seminara, Mitul Shah, Tameka Shelford, Min-Ho Shin, Katerina Shulman, Sabina Sieri, Martha L. Slattery, Melissa C. Southey, Zsofia K. Stadler, Christa Stegmaier, Yu-Ru Su, Catherine M. Tangen, Stephen N. Thibodeau, Duncan C. Thomas, Sushma S. Thomas, Amanda E. Toland, Antonia Trichopoulou, Cornelia M. Ulrich, David J. Van Den Berg, Franzel J. B. van Duijnhoven, Bethany Van Guelpen, Henk van Kranen, Joseph Vijai, Kala Visvanathan, Pavel Vodicka, Ludmila Vodickova, Veronika Vymetalkova, Korbinian Weigl, Stephanie J. Weinstein, Emily White, Aung Ko Win, C. Roland Wolf, Alicja Wolk, Michael O. Woods, Anna H. Wu, Syed H. Zaidi, Brent W. Zanke, Qing Zhang, Wei Zheng, Peter C. Scacheri, John D. Potter, Michael C. Bassik, Anshul Kundaje, Graham Casey, Victor Moreno, Goncalo R. Abecasis, Deborah A. Nickerson, Stephen B. Gruber, Li Hsu, Ulrike Peters

ABSTRACT

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development. More... »

PAGES

76-87

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    1

    VOLUME

    51

    Author Affiliations

  • Fred Hutchinson Cancer Research Center
  • University of Michigan–Ann Arbor
  • Moffitt Cancer Center
  • University of Southern California
  • Stanford University
  • Case Western Reserve University
  • University of Washington
  • National Institutes of Health
  • University of Barcelona
  • University of Minnesota
  • German Cancer Research Center
  • National and Kapodistrian University of Athens
  • University of North Carolina at Chapel Hill
  • Centre Hospitalier Universitaire de Nantes
  • University of Leeds
  • University of Utah
  • German Institute of Human Nutrition
  • Medical University of Vienna
  • Royal Melbourne Hospital
  • Kaiser Permanente
  • American Cancer Society
  • Harvard University
  • University Medical Center Hamburg-Eppendorf
  • University of Murcia
  • Chonnam National University Hospital
  • Imperial College London
  • The Ohio State University
  • Johns Hopkins University
  • Translational Genomics Research Institute
  • University of Cambridge
  • Cancer Council Victoria
  • Wageningen University & Research
  • Michigan Medicine
  • University of Tasmania
  • International Agency For Research On Cancer
  • University of Toronto
  • National Cancer Institute
  • University of Hawaii at Manoa
  • Umeå University
  • New York University
  • Seoul National University
  • Ontario Institute for Cancer Research
  • University of Oxford
  • Bellvitge University Hospital
  • University of Melbourne
  • University of North Carolina System
  • Chonnam National University Hwasun Hospital
  • Karolinska Institute
  • Baylor College of Medicine
  • National University of Singapore
  • Carmel Medical Center
  • Kiel University
  • Mayo Clinic
  • National Institute for Health and Welfare
  • University of Leon
  • Academy of Sciences of the Czech Republic
  • Cornell University
  • Dana–Farber Cancer Institute
  • University of Turin
  • Memorial University of Newfoundland
  • Institut Gustave Roussy
  • Vanderbilt University
  • Technion – Israel Institute of Technology
  • University of Granada
  • University Hospital Schleswig-Holstein
  • University of Pittsburgh Medical Center
  • Chonnam National University
  • Hillel Yaffe Medical Center
  • Istituto Nazionale dei Tumori
  • Memorial Sloan Kettering Cancer Center
  • Krebsregister Saarland
  • Mayo Clinic
  • National Institute for Public Health and the Environment
  • Charles University
  • Heidelberg University
  • University of Dundee
  • Uppsala University
  • University of Virginia
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-018-0286-6

    DOI

    http://dx.doi.org/10.1038/s41588-018-0286-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1110204867

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30510241


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