Advanced

A genome-wide association study on copy-number variation identifies a 11q11 loss as a candidate susceptibility variant for colorectal cancer

Fernandez-Rozadilla, C.; Cazier, J. B.; Tomlinson, I.; Brea-Fernandez, A.; Lamas, M. J.; Baiget, M.; Lopez-Fernandez, L. A.; Clofent, J.; Bujanda, L. and Gonzalez, D., et al. (2014) In Human Genetics 133(5). p.525-534
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.... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Genetics
volume
133
issue
5
pages
525 - 534
publisher
Springer
external identifiers
  • wos:000334519900005
  • scopus:84899650780
ISSN
1432-1203
DOI
10.1007/s00439-013-1390-4
language
English
LU publication?
yes
id
22230468-1dee-4db3-b06b-eacb0e474959 (old id 4487992)
date added to LUP
2014-07-01 07:33:49
date last changed
2017-11-12 03:40:30
@article{22230468-1dee-4db3-b06b-eacb0e474959,
  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.},
  author       = {Fernandez-Rozadilla, C. and Cazier, J. B. and Tomlinson, I. and Brea-Fernandez, A. and Lamas, M. J. and Baiget, M. and Lopez-Fernandez, L. A. and Clofent, J. and Bujanda, L. and Gonzalez, D. and de Castro, L. and Hemminki, Kari and Bessa, X. and Andreu, M. and Jover, R. and Xicola, R. and Llor, X. and Moreno, V. and Castells, A. and Castellvi-Bel, S. and Carracedo, A. and Ruiz-Ponte, C.},
  issn         = {1432-1203},
  language     = {eng},
  number       = {5},
  pages        = {525--534},
  publisher    = {Springer},
  series       = {Human Genetics},
  title        = {A genome-wide association study on copy-number variation identifies a 11q11 loss as a candidate susceptibility variant for colorectal cancer},
  url          = {http://dx.doi.org/10.1007/s00439-013-1390-4},
  volume       = {133},
  year         = {2014},
}