A genome-wide association study on copy-number variation identifies a 11q11 loss as a candidate susceptibility variant for colorectal cancer.
Hum Genet
; 133(5): 525-34, 2014 May.
Article
em En
| MEDLINE
| ID: mdl-24218287
ABSTRACT
Colorectal cancer (CRC) is a complex disease, and therefore its development is determined by the combination of both environmental factors and genetic variants. Although genome-wide association studies (GWAS) of SNP variation have conveniently identified 20 genetic variants so far, a significant proportion of the observed heritability is yet to be explained. Common copy-number variants (CNVs) are one of the most important genomic sources of variability, and hence a potential source to explain part of this missing genetic fraction. Therefore, we have performed a GWAS on CNVs to explore the relationship between common structural variation and CRC development. Phase 1 of the GWAS consisted of 881 cases and 667 controls from a Spanish cohort. Copy-number status was validated by quantitative PCR for each of those common CNVs potentially associated with CRC in phase I. Subsequently, SNPs were chosen as proxies for the validated CNVs for phase II replication (1,342 Spanish cases and 1,874 Spanish controls). Four common CNVs were found to be associated with CRC and were further replicated in Phase II. Finally, we found that SNP rs1944682, tagging a 11q11 CNV, was nominally associated with CRC susceptibility (p value = 0.039; OR = 1.122). This locus has been previously related to extreme obesity phenotypes, which could suggest a relationship between body weight and CRC susceptibility.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 11
/
Neoplasias Colorretais
/
Dosagem de Genes
/
Predisposição Genética para Doença
/
Estudo de Associação Genômica Ampla
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Hum Genet
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Espanha