Association analyses identify 31 new risk loci for colorectal cancer susceptibility.
;
Maria Timofeeva ;
Ceres Fernandez-Rozadilla ;
Peter Broderick ;
James Studd ;
Juan Fernandez-Tajes;
Susan Farrington ;
Victoria Svinti ;
Claire Palles;
Giulia Orlando;
+89 more...
Amit Sud ;
Amy Holroyd;
Steven Penegar;
Evropi Theodoratou;
Peter Vaughan-Shaw;
Harry Campbell;
Lina Zgaga;
Caroline Hayward ;
Archie Campbell ;
Sarah Harris;
Ian J Deary;
John Starr;
Laura Gatcombe;
Maria Pinna;
Sarah Briggs;
Lynn Martin ;
Emma Jaeger;
Archana Sharma-Oates;
James East ;
Simon Leedham;
Roland Arnold;
Elaine Johnstone;
Haitao Wang;
David Kerr;
Rachel Kerr;
Tim Maughan;
Richard Kaplan ;
Nada Al-Tassan ;
Kimmo Palin ;
Ulrika A Hänninen;
Tatiana Cajuso;
Tomas Tanskanen;
Johanna Kondelin;
Eevi Kaasinen;
Antti-Pekka Sarin;
Johan G Eriksson;
Harri Rissanen;
Paul Knekt;
Eero Pukkala;
Pekka Jousilahti;
Veikko Salomaa ;
Samuli Ripatti;
Aarno Palotie;
Laura Renkonen-Sinisalo;
Anna Lepistö;
Jan Böhm;
Jukka-Pekka Mecklin;
Daniel D Buchanan ;
Aung-Ko Win ;
John Hopper;
Mark E Jenkins ;
Noralane M Lindor;
Polly A Newcomb;
Steven Gallinger;
David Duggan;
Graham Casey;
Per Hoffmann;
Markus M Nöthen;
Karl-Heinz Jöckel;
Douglas F Easton ;
Paul DP Pharoah ;
Julian Peto ;
Federico Canzian;
Anthony Swerdlow;
Rosalind A Eeles ;
Zsofia Kote-Jarai;
Kenneth Muir ;
Nora Pashayan ;
PRACTICAL consortium;
Andrea Harkin ;
Karen Allan;
John McQueen;
James Paul ;
Timothy Iveson;
Mark Saunders;
Katja Butterbach;
Jenny Chang-Claude;
Michael Hoffmeister;
Hermann Brenner;
Iva Kirac;
Petar Matošević;
Philipp Hofer ;
Stefanie Brezina ;
Andrea Gsur;
Jeremy P Cheadle ;
Lauri A Aaltonen;
Ian Tomlinson ;
Richard S Houlston ;
Malcolm G Dunlop;
(2019)
Association analyses identify 31 new risk loci for colorectal cancer susceptibility.
Nature Communications, 10 (1).
2154-.
ISSN 2041-1723
DOI: 10.1038/s41467-019-09775-w
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.
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