Journal article

Multiple Common Susceptibility Variants near BMP Pathway Loci GREM1, BMP4, and BMP2 Explain Part of the Missing Heritability of Colorectal Cancer

Ian PM Tomlinson, Luis G Carvajal-Carmona, Sara E Dobbins, Albert Tenesa, Angela M Jones, Kimberley Howarth, Claire Palles, Peter Broderick, Emma EM Jaeger, Susan Farrington, Annabelle Lewis, James GD Prendergast, Alan M Pittman, Evropi Theodoratou, Bianca Olver, Marion Walker, Steven Penegar, Ella Barclay, Nicola Whiffin, Lynn Martin Show all

PLoS Genetics | PUBLIC LIBRARY SCIENCE | Published : 2011

Abstract

Genome-wide association studies (GWAS) have identified 14 tagging single nucleotide polymorphisms (tagSNPs) that are associated with the risk of colorectal cancer (CRC), and several of these tagSNPs are near bone morphogenetic protein (BMP) pathway loci. The penalty of multiple testing implicit in GWAS increases the attraction of complementary approaches for disease gene discovery, including candidate gene- or pathway-based analyses. The strongest candidate loci for additional predisposition SNPs are arguably those already known both to have functional relevance and to be involved in disease risk. To investigate this proposition, we searched for novel CRC susceptibility variants close to the..

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Grants

Awarded by Wellcome Trust Centre for Human Genetics, Oxford


Awarded by Medical Research Council


Awarded by Scottish Executive Chief Scientist's Office


Awarded by National Cancer Institute, National Institutes of Health


Awarded by Australian Colorectal Cancer Family Registry


Awarded by USC Familial Colorectal Neoplasia Collaborative Group


Awarded by Mayo Clinic Cooperative Family Registry for Colon Cancer Studies


Awarded by Ontario Registry for Studies of Familial Colorectal Cancer


Awarded by Seattle Colorectal Cancer Family Registry


Awarded by University of Hawaii Colorectal Cancer Family Registry


Awarded by Cancer Research UK Fellowship


Awarded by NATIONAL CANCER INSTITUTE


Awarded by Cancer Research UK


Awarded by The Francis Crick Institute


Awarded by Chief Scientist Office


Awarded by Tenovus Cancer Care


Funding Acknowledgements

Cancer Research UK provided principal funding for this study individually to IPM Tomlinson, MG Dunlop, RS Houlston, P Pharoah, and J Cheadle. Additional funding was provided by the Oxford Comprehensive Biomedical Research Centre (to IPM Tomlinson) and the EU FP7 CHIBCHA grant (to LG Carvajal-Carmona and IPM Tomlinson). Core infrastructure support to the Wellcome Trust Centre for Human Genetics, Oxford, was provided by grant 075491/Z/04. Additional funding (to MG Dunlop) was provided by the Medical Research Council (G0000657-53203), CORE, and Scottish Executive Chief Scientist's Office (K/OP/2/2/D333, CZB/4/449). The Colon Cancer Family Registry was supported by the National Cancer Institute, National Institutes of Health, under Request for Application #CA-95-011, and through cooperative agreements with the Australian Colorectal Cancer Family Registry (UO1 CA097735), the USC Familial Colorectal Neoplasia Collaborative Group (UO1 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (UO1 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (UO1 CA074783), Seattle Colorectal Cancer Family Registry (UO1 CA074794), and The University of Hawaii Colorectal Cancer Family Registry (UO1 CA074806). E Theodoratou was funded by a Cancer Research UK Fellowship (C31250/A10107). COIN and COIN-B were funded by the UK Medical Research Council. COIN sample analysis (J Cheadle) was also funded by Cancer Research Wales, Tenovus & Wales Gene Park. P Pharoah is a Cancer Research UK Senior Clinical Research Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.