Functional annotation of colon cancer risk SNPs

Lijing Yao, Yu Gyoung Tak, Benjamin P. Berman, Peggy J. Farnham*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with increased risk for CRC. A molecular understanding of the functional consequences of this genetic variation has been complicated because each GWAS SNP is a surrogate for hundreds of other SNPs, most of which are located in non-coding regions. Here we use genomic and epigenomic information to test the hypothesis that the GWAS SNPs and/or correlated SNPs are in elements that regulate gene expression, and identify 23 promoters and 28 enhancers. Using gene expression data from normal and tumour cells, we identify 66 putative target genes of the risk-associated enhancers (10 of which were also identified by promoter SNPs). Employing CRISPR nucleases, we delete one risk-associated enhancer and identify genes showing altered expression. We suggest that similar studies be performed to characterize all CRC risk-associated enhancers.

Original languageAmerican English
Article number5114
JournalNature Communications
StatePublished - 2014
Externally publishedYes

Bibliographical note

Funding Information:
We thank the UCSD Roadmap Epigenome Mapping Center for use of the H3K27Ac and RNA-seq data from sigmoid colon prior to publication by the Roadmap Epigenomics Consortium (, Sushma Iyengar and Michael Kahn for use of their SW480 ChIP-seq data, Adam Blattler, Fides Lay and Peter Jones for use of their HCT116 RNA-seq data, David Segal and Mital Bhakta for guidance and assistance with the CRISPR technology, the DNA Production Facility at the USC Epi-genome Center for library construction and sequencing of RNA samples, and the USC high performance computing and communications center. The HCT116 H3K27Ac ChIP-seq data was produced in the Farnham lab as part of the ENCODE Consortium15. This work was supported in part by 5R21HG006761, U01 ES017154 and P30CA014089 from the National Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2014 Macmillan Publishers Limited. All rights reserved.


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