@article{3077371,
    title = "Discovery of common and rare genetic risk variants for colorectal cancer",
    author = "Huyghe, J.R. and Bien, S.A. and Harrison, T.A. and Kang, H.M. and Chen, S. and Schmit, S.L. and Conti, D.V. and Qu, C. and Jeon, J. and Edlund, C.K. and Greenside, P. and Wainberg, M. and Schumacher, F.R. and Smith, J.D. and Levine, D.M. and Nelson, S.C. and Sinnott-Armstrong, N.A. and Albanes, D. and Alonso, M.H. and Anderson, K. and Arnau-Collell, C. and Arndt, V. and Bamia, C. and Banbury, B.L. and Baron, J.A. and Berndt, S.I. and Bézieau, S. and Bishop, D.T. and Boehm, J. and Boeing, H. and Brenner, H. and Brezina, S. and Buch, S. and Buchanan, D.D. and Burnett-Hartman, A. and Butterbach, K. and Caan, B.J. and Campbell, P.T. and Carlson, C.S. and Castellví-Bel, S. and Chan, A.T. and Chang-Claude, J. and Chanock, S.J. and Chirlaque, M.-D. and Cho, S.H. and Connolly, C.M. and Cross, A.J. and Cuk, K. and Curtis, K.R. and de la Chapelle, A. and Doheny, K.F. and Duggan, D. and Easton, D.F. and Elias, S.G. and Elliott, F. and English, D.R. and Feskens, E.J.M. and Figueiredo, J.C. and Fischer, R. and FitzGerald, L.M. and Forman, D. and Gala, M. and Gallinger, S. and Gauderman, W.J. and Giles, G.G. and Gillanders, E. and Gong, J. and Goodman, P.J. and Grady, W.M. and Grove, J.S. and Gsur, A. and Gunter, M.J. and Haile, R.W. and Hampe, J. and Hampel, H. and Harlid, S. and Hayes, R.B. and Hofer, P. and Hoffmeister, M. and Hopper, J.L. and Hsu, W.-L. and Huang, W.-Y. and Hudson, T.J. and Hunter, D.J. and Ibañez-Sanz, G. and Idos, G.E. and Ingersoll, R. and Jackson, R.D. and Jacobs, E.J. and Jenkins, M.A. and Joshi, A.D. and Joshu, C.E. and Keku, T.O. and Key, T.J. and Kim, H.R. and Kobayashi, E. and Kolonel, L.N. and Kooperberg, C. and Kühn, T. and Küry, S. and Kweon, S.-S. and Larsson, S.C. and Laurie, C.A. and Le Marchand, L. and Leal, S.M. and Lee, S.C. and Lejbkowicz, F. and Lemire, M. and Li, C.I. and Li, L. and Lieb, W. and Lin, Y. and Lindblom, A. and Lindor, N.M. and Ling, H. and Louie, T.L. and Männistö, S. and Markowitz, S.D. and Martín, V. and Masala, G. and McNeil, C.E. and Melas, M. and Milne, R.L. and Moreno, L. and Murphy, N. and Myte, R. and Naccarati, A. and Newcomb, P.A. and Offit, K. and Ogino, S. and Onland-Moret, N.C. and Pardini, B. and Parfrey, P.S. and Pearlman, R. and Perduca, V. and Pharoah, P.D.P. and Pinchev, M. and Platz, E.A. and Prentice, R.L. and Pugh, E. and Raskin, L. and Rennert, G. and Rennert, H.S. and Riboli, E. and Rodríguez-Barranco, M. and Romm, J. and Sakoda, L.C. and Schafmayer, C. and Schoen, R.E. and Seminara, D. and Shah, M. and Shelford, T. and Shin, M.-H. and Shulman, K. and Sieri, S. and Slattery, M.L. and Southey, M.C. and Stadler, Z.K. and Stegmaier, C. and Su, Y.-R. and Tangen, C.M. and Thibodeau, S.N. and Thomas, D.C. and Thomas, S.S. and Toland, A.E. and Trichopoulou, A. and Ulrich, C.M. and Van Den Berg, D.J. and van Duijnhoven, F.J.B. and Van Guelpen, B. and van Kranen, H. and Vijai, J. and Visvanathan, K. and Vodicka, P. and Vodickova, L. and Vymetalkova, V. and Weigl, K. and Weinstein, S.J. and White, E. and Win, A.K. and Wolf, C.R. and Wolk, A. and Woods, M.O. and Wu, A.H. and Zaidi, S.H. and Zanke, B.W. and Zhang, Q. and Zheng, W. and Scacheri, P.C. and Potter, J.D. and Bassik, M.C. and Kundaje, A. and Casey, G. and Moreno, V. and Abecasis, G.R. and Nickerson, D.A. and Gruber, S.B. and Hsu, L. and Peters, U.",
    journal = "Nature Genetics",
    year = "2019",
    volume = "51",
    number = "1",
    pages = "76-87",
    publisher = "Nature Publishing Group",
    issn = "1061-4036, 1546-1718",
    doi = "10.1038/s41588-018-0286-6",
    keywords = "chd1 protein;  long untranslated RNA;  protein;  unclassified drug;  yap protein;  long untranslated RNA, Article;  cancer patient;  cancer risk;  colorectal cancer;  controlled study;  gene frequency;  gene identification;  gene linkage disequilibrium;  gene locus;  genetic association;  genetic risk;  genetic variability;  genome-wide association study;  haplotype;  hedgehog signaling;  heritability;  hippo signaling;  human;  human tissue;  indel mutation;  major clinical study;  priority journal;  single nucleotide polymorphism;  whole genome sequencing;  aged;  case control study;  colorectal tumor;  female;  genetic predisposition;  genetics;  genotype;  male;  meta analysis;  middle aged;  procedures;  risk factor;  signal transduction, Aged;  Case-Control Studies;  Colorectal Neoplasms;  Female;  Genetic Predisposition to Disease;  Genome-Wide Association Study;  Genotype;  Humans;  Male;  Middle Aged;  Polymorphism, Single Nucleotide;  Risk Factors;  RNA, Long Noncoding;  Signal Transduction",
    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. © 2018, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply."
}