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Association analyses identify 31 new risk loci for colorectal cancer susceptibility

Law, Philip J., Timofeeva, Maria, Fernandez-Rozadilla, Ceres, Broderick, Peter, Studd, James, Fernandez-Tajes, Juan, Farrington, Susan, Svinti, Victoria, Palles, Claire, Orlando, Giulia, Sud, Amit, Holroyd, Amy, Penegar, Steven, Theodoratou, Evropi, Vaughan-Shaw, Peter, Campbell, Harry, Zgaga, Lina, Hayward, Caroline, Campbell, Archie, Harris, Sarah, Deary, Ian J., Starr, John, Gatcombe, Laura, Pinna, Maria, Briggs, Sarah, Martin, Lynn, Jaeger, Emma, Sharma-Oates, Archana, East, James, Leedham, Simon, Arnold, Roland, Johnstone, Elaine, Wang, Haitao, Kerr, David, Kerr, Rachel, Maughan, Tim, Kaplan, Richard, Al-Tassan, Nada, Palin, Kimmo, Hänninen, Ulrika A., Cajuso, Tatiana, Tanskanen, Tomas, Kondelin, Johanna, Kaasinen, Eevi, Sarin, Antti-Pekka, Eriksson, Johan G., Rissanen, Harri, Knekt, Paul, Pukkala, Eero, Jousilahti, Pekka, Salomaa, Veikko, Ripatti, Samuli, Palotie, Aarno, Renkonen-Sinisalo, Laura, Lepistö, Anna, Böhm, Jan, Mecklin, Jukka-Pekka, Buchanan, Daniel D., Win, Aung-Ko, Hopper, John, Jenkins, Mark E., Lindor, Noralane M., Newcomb, Polly A., Gallinger, Steven, Duggan, David, Casey, Graham, Hoffmann, Per, Nöthen, Markus M., Jöckel, Karl-Heinz, Easton, Douglas F., Pharoah, Paul D. P., Peto, Julian, Canzian, Federico, Swerdlow, Anthony, Eeles, Rosalind A., Kote-Jarai, Zsofia, Muir, Kenneth, Pashayan, Nora, Harkin, Andrea, Allan, Karen, McQueen, John, Paul, James, Iveson, Timothy, Saunders, Mark, Butterbach, Katja, Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Kirac, Iva, Matošević, Petar, Hofer, Philipp, Brezina, Stefanie, Gsur, Andrea, Cheadle, Jeremy P., Aaltonen, Lauri A., Tomlinson, Ian, Houlston, Richard S. and Dunlop, Malcolm G. 2019. Association analyses identify 31 new risk loci for colorectal cancer susceptibility. Nature Communications 10 , 2154. 10.1038/s41467-019-09775-w

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: The PRACTICAL consortium
Publisher: Nature Research
ISSN: 2041-1723
Date of First Compliant Deposit: 30 May 2019
Date of Acceptance: 29 March 2019
Last Modified: 21 May 2020 16:19
URI: http://orca-mwe.cf.ac.uk/id/eprint/122995

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