Ερευνητικό υλικό ΕΚΠΑ

Discovery of common and rare genetic risk variants for colorectal cancer

Αγγλικά

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.

2019

Huyghe, J.R.
Bien, S.A.
Harrison, T.A.
Kang, H.M.
Chen, S.
Schmit, S.L.
Conti, D.V.
Qu, C.
Jeon, J.
Edlund, C.K.
Greenside, P.
Wainberg, M.
Schumacher, F.R.
Smith, J.D.
Levine, D.M.
Nelson, S.C.
Sinnott-Armstrong, N.A.
Albanes, D.
Alonso, M.H.
Anderson, K.
Arnau-Collell, C.
Arndt, V.
Bamia, C.
Banbury, B.L.
Baron, J.A.
Berndt, S.I.
Bézieau, S.
Bishop, D.T.
Boehm, J.
Boeing, H.
Brenner, H.
Brezina, S.
Buch, S.
Buchanan, D.D.
Burnett-Hartman, A.
Butterbach, K.
Caan, B.J.
Campbell, P.T.
Carlson, C.S.
Castellví-Bel, S.
Chan, A.T.
Chang-Claude, J.
Chanock, S.J.
Chirlaque, M.-D.
Cho, S.H.
Connolly, C.M.
Cross, A.J.
Cuk, K.
Curtis, K.R.
de la Chapelle, A.
Doheny, K.F.
Duggan, D.
Easton, D.F.
Elias, S.G.
Elliott, F.
English, D.R.
Feskens, E.J.M.
Figueiredo, J.C.
Fischer, R.
FitzGerald, L.M.
Forman, D.
Gala, M.
Gallinger, S.
Gauderman, W.J.
Giles, G.G.
Gillanders, E.
Gong, J.
Goodman, P.J.
Grady, W.M.
Grove, J.S.
Gsur, A.
Gunter, M.J.
Haile, R.W.
Hampe, J.
Hampel, H.
Harlid, S.
Hayes, R.B.
Hofer, P.
Hoffmeister, M.
Hopper, J.L.
Hsu, W.-L.
Huang, W.-Y.
Hudson, T.J.
Hunter, D.J.
Ibañez-Sanz, G.
Idos, G.E.
Ingersoll, R.
Jackson, R.D.
Jacobs, E.J.
Jenkins, M.A.
Joshi, A.D.
Joshu, C.E.
Keku, T.O.
Key, T.J.
Kim, H.R.
Kobayashi, E.
Kolonel, L.N.
Kooperberg, C.
Kühn, T.
Küry, S.
Kweon, S.-S.
Larsson, S.C.
Laurie, C.A.
Le Marchand, L.
Leal, S.M.
Lee, S.C.
Lejbkowicz, F.
Lemire, M.
Li, C.I.
Li, L.
Lieb, W.
Lin, Y.
Lindblom, A.
Lindor, N.M.
Ling, H.
Louie, T.L.
Männistö, S.
Markowitz, S.D.
Martín, V.
Masala, G.
McNeil, C.E.
Melas, M.
Milne, R.L.
Moreno, L.
Murphy, N.
Myte, R.
Naccarati, A.
Newcomb, P.A.
Offit, K.
Ogino, S.
Onland-Moret, N.C.
Pardini, B.
Parfrey, P.S.
Pearlman, R.
Perduca, V.
Pharoah, P.D.P.
Pinchev, M.
Platz, E.A.
Prentice, R.L.
Pugh, E.
Raskin, L.
Rennert, G.
Rennert, H.S.
Riboli, E.
Rodríguez-Barranco, M.
Romm, J.
Sakoda, L.C.
Schafmayer, C.
Schoen, R.E.
Seminara, D.
Shah, M.
Shelford, T.
Shin, M.-H.
Shulman, K.
Sieri, S.
Slattery, M.L.
Southey, M.C.
Stadler, Z.K.
Stegmaier, C.
Su, Y.-R.
Tangen, C.M.
Thibodeau, S.N.
Thomas, D.C.
Thomas, S.S.
Toland, A.E.
Trichopoulou, A.
Ulrich, C.M.
Van Den Berg, D.J.
van Duijnhoven, F.J.B.
Van Guelpen, B.
van Kranen, H.
Vijai, J.
Visvanathan, K.
Vodicka, P.
Vodickova, L.
Vymetalkova, V.
Weigl, K.
Weinstein, S.J.
White, E.
Win, A.K.
Wolf, C.R.
Wolk, A.
Woods, M.O.
Wu, A.H.
Zaidi, S.H.
Zanke, B.W.
Zhang, Q.
Zheng, W.
Scacheri, P.C.
Potter, J.D.
Bassik, M.C.
Kundaje, A.
Casey, G.
Moreno, V.
Abecasis, G.R.
Nickerson, D.A.
Gruber, S.B.
Hsu, L.
Peters, U.

Nature Genetics

Nature Publishing Group

51

1

76-87

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

https://doi.org/10.1038/s41588-018-0286-6

10.1038/s41588-018-0286-6

https://pergamos.lib.uoa.gr/uoa/dl/object/3077371