Functional annotation of colon cancer risk SNPs.
Functional annotation of colon cancer risk SNPs.
复制标题
DOI：
10.1038/ncomms6114
复制
发表时间：
2014-09-30
影响因子：
16.6
通讯作者：
Farnham, Peggy J.
中科院分区：
文献类型：
--
作者：
Yao, Lijing;Tak, Yu Gyoung;Berman, Benjamin P.;Farnham, Peggy J.
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. Previous studies identified genetic variants associated with colorectal cancer (CRC), but the functional consequences of these genetic risk factors remain poorly understood. Here, the authors report that CRC risk variants reside in promoters and enhancers and could increase colon cancer risk through gene expression regulation.
登录
查看更多内容
影响因子：
16
作者：
Calo, Eliezer;Wysocka, Joanna
通讯作者：
Wysocka, Joanna
影响因子：
14.9
作者：
Blahnik KR;Dou L;O'Geen H;McPhillips T;Xu X;Cao AR;Iyengar S;Nicolet CM;Ludäscher B;Korf I;Farnham PJ
通讯作者：
Farnham PJ
影响因子：
4.5
作者：
Hazelett DJ;Rhie SK;Gaddis M;Yan C;Lakeland DL;Coetzee SG;Ellipse/GAME-ON consortium;Practical consortium;Henderson BE;Noushmehr H;Cozen W;Kote-Jarai Z;Eeles RA;Easton DF;Haiman CA;Lu W;Farnham PJ;Coetzee GA
通讯作者：
Coetzee GA
影响因子：
30.8
作者：
Dunlop MG;Dobbins SE;Farrington SM;Jones AM;Palles C;Whiffin N;Tenesa A;Spain S;Broderick P;Ooi LY;Domingo E;Smillie C;Henrion M;Frampton M;Martin L;Grimes G;Gorman M;Semple C;Ma YP;Barclay E;Prendergast J;Cazier JB;Olver B;Penegar S;Lubbe S;Chander I;Carvajal-Carmona LG;Ballereau S;Lloyd A;Vijayakrishnan J;Zgaga L;Rudan I;Theodoratou E;Colorectal Tumour Gene Identification (CORGI) Consortium;Starr JM;Deary I;Kirac I;Kovacević D;Aaltonen LA;Renkonen-Sinisalo L;Mecklin JP;Matsuda K;Nakamura Y;Okada Y;Gallinger S;Duggan DJ;Conti D;Newcomb P;Hopper J;Jenkins MA;Schumacher F;Casey G;Easton D;Shah M;Pharoah P;Lindblom A;Liu T;Swedish Low-Risk Colorectal Cancer Study Group;Smith CG;West H;Cheadle JP;COIN Collaborative Group;Midgley R;Kerr DJ;Campbell H;Tomlinson IP;Houlston RS
通讯作者：
Houlston RS
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.