TY - JOUR
T1 - Association analyses identify 31 new risk loci for colorectal cancer susceptibility
AU - Law, Philip J
AU - Timofeeva, Maria
AU - Fernandez-Rozadilla, Ceres
AU - Broderick, Peter
AU - Studd, James
AU - Fernandez-Tajes, Juan
AU - Farrington, Susan
AU - Svinti MacLeod, Victoria
AU - Palles, Claire
AU - Orlando, Giulia
AU - Sud, Amit
AU - Holroyd, Amy
AU - Penegar, Steven
AU - Theodoratou, Evropi
AU - Vaughan-Shaw, Peter
AU - Campbell, Harry
AU - Zgaga, Lina
AU - Hayward, Caroline
AU - Campbell, Archie
AU - Harris, Sarah
AU - Deary, Ian J.
AU - Starr, John
AU - Laura, Gatcombe
AU - Pinna, Maria
AU - Briggs, Sarah
AU - Martin, Lynn
AU - Jaeger, Emma
AU - Sharma-Oates, Archana
AU - East, James
AU - Leedham, Simon
AU - Arnold, Roland
AU - Johnstone, Elaine
AU - Wang, Haitao
AU - Kerr, David
AU - Kerr, Rachel
AU - Maughan, Tim
AU - Kaplan, Richard
AU - Al-Tassan, Nada
AU - Palin, Kimmo
AU - Hanninen, Ulrika A.
AU - Cajuso, Tatiana
AU - Tanskanen, Tomas
AU - Kondelin, Johanna
AU - Kaasinen, Eevi
AU - Sarin, Antti-Pekka
AU - Eriksson, Johan G.
AU - Rissanen, Harri
AU - Knekt, Paul
AU - Pukkala, Eero
AU - Jousilahti, Pekka
AU - Salomaa, Veikko
AU - Ripatti, Samuli
AU - Palotie, Aarno
AU - Renkonen-Sinisalo, Laura
AU - Lepisto, Anna
AU - Böhm, Jan
AU - Mecklin, Jukka-Pekka
AU - Buchanan, Daniel D.
AU - Win, Aung-Ko
AU - Hopper, John
AU - Jenkins, Mark E.
AU - Lindor, Noralane M.
AU - Newcomb, Polly A
AU - Gallinger, Steven
AU - Duggan, David
AU - Casey, Graham
AU - Hoffman, Per
AU - Nöthen, Markus M
AU - Jöckel, Karl-Heinz
AU - Easton, Douglas F.
AU - Pharoah, Paul D P
AU - Peto, Julian
AU - Canzian, Federico
AU - Swerdlow, Anthony J.
AU - Eeles, Rosalind A
AU - Kote-Jarai, Zsofia
AU - Muir, Kenneth R.
AU - Pashayan, Nora
AU - PRACTICAL Consortium
AU - Harkin, Andrea
AU - Allan, Karen
AU - McQueen, John
AU - Paul, James
AU - Iveson , Tim
AU - Saunders, Mark
AU - Butterbach, Katja
AU - Chang-Claude, Jenny
AU - Hoffmeister, Michael
AU - Brenner, Hermann
AU - Kirac, Iva
AU - Matošević, Petar
AU - Hofer, Philipp
AU - Brezina, Stefanie
AU - Gsur, Andrea
AU - Cheadle, Jeremy P.
AU - Aaltonen, Lauri
AU - Tomlinson, Ian
AU - Houlston, Richard S
AU - Dunlop, Malcolm G.
N1 - will be published oa
PY - 2019/5/14
Y1 - 2019/5/14
N2 - Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
AB - Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
KW - cancer genetics
KW - cancer genomics
KW - colorectal cancer
KW - genome-wide association studies
UR - https://www.nature.com/articles/s41467-019-09775-w#Sec28
U2 - 10.1038/s41467-019-09775-w
DO - 10.1038/s41467-019-09775-w
M3 - Article
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
M1 - 2154
ER -