Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/148425
Title: Multiple Common Susceptibility Variants near BMP Pathway Loci GREM1, BMP4, and BMP2 Explain Part of the Missing Heritability of Colorectal Cancer
Author: Castells Garangou, Antoni
Castellví-Bel, Sergi
The COGENT Consortium
The CORGI Collaborators
The EPICOLON Consortium
Keywords: Càncer colorectal
Genètica molecular
Colorectal cancer
Molecular genetics
Issue Date: 2-Jun-2011
Publisher: Public Library of Science (PLoS)
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 BMP pathway genes GREM1 (15q13.3), BMP4 (14q22.2), and BMP2 (20p12.3) using sample sets totalling 24,910 CRC cases and 26,275 controls. We identified new, independent CRC predisposition SNPs close to BMP4 (rs1957636, P = 3.93×10−10) and BMP2 (rs4813802, P = 4.65×10−11). Near GREM1, we found using fine-mapping that the previously-identified association between tagSNP rs4779584 and CRC actually resulted from two independent signals represented by rs16969681 (P = 5.33×10−8) and rs11632715 (P = 2.30×10−10). As low-penetrance predisposition variants become harder to identify owing to small effect sizes and/or low risk allele frequencies approaches based on informed candidate gene selection may become increasingly attractive. Our data emphasise that genetic fine-mapping studies can deconvolute associations that have arisen owing to independent correlation of a tagSNP with more than one functional SNP, thus explaining some of the apparently missing heritability of common diseases.
Note: Reproducció del document publicat a: https://doi.org/10.1371/journal.pgen.1002105
It is part of: PLoS Genetics, 2011, vol. 7, num. 6, p. e1002105
URI: http://hdl.handle.net/2445/148425
Related resource: https://doi.org/10.1371/journal.pgen.1002105
ISSN: 1553-7390
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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