Enrichment of inflammatory bowel disease and colorectal cancer risk variants in colon expression quantitative trait loci.
Enrichment of inflammatory bowel disease and colorectal cancer risk variants in colon expression quantitative trait loci.
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DOI：
10.1186/s12864-015-1292-z
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发表时间：
2015-02-27
期刊：
影响因子：
4.4
通讯作者：
Kupfer SS
中科院分区：
文献类型：
--
作者：
Hulur I;Gamazon ER;Skol AD;Xicola RM;Llor X;Onel K;Ellis NA;Kupfer SS
全基因组关联研究（GWAS）已经鉴定了与结肠疾病（包括炎症性肠病（IBD）和结直肠癌（CRC））相关的单核苷酸多态性（SNP）。然而，许多这些SNP的功能作用在很大程度上是未知的，缺乏组织特异性资源。表达数量性状基因座（eQTL）定位确定疾病相关SNP的靶基因。这项研究提供了一个全面的eQTL图谱的远端结肠样品从40个健康的非洲裔美国人，并证明其相关性GWAS的结肠疾病。8.4测试了100万个估算的SNP与代表12，363个独特基因的16，252个表达探针的关联。以0.01的错误发现率（FDR）鉴定了1，941个显著的顺式eQTL，对应于122个独立信号。总体而言，在结肠顺式eQTL中，IBD（克罗恩病[CD]和溃疡性结肠炎[UC]）和CRC以及2型糖尿病和体重指数的GWAS变体显著富集。ERAP 2、ADCY 3、INPP 5E、UBA 7、SFMBT 1、NXPE 1和REXO 2被鉴定为IBD相关变体的靶基因。与CRC相关的eQTL rs3802842与C11 orf 93（COLCA 2）的表达相关。证实了在转录起始位点附近和活性组蛋白标记的结肠eQTL的富集，并且鉴定了具有高群体分化的eQTL。通过对人类结肠eQTL的全面研究，本研究确定了IBD和CRC相关遗传变异的新靶基因。此外，结肠eQTL的生物信息学表征提供了一种组织特异性工具，以提高对不同种族之间疾病生物学差异的理解。本文的在线版本（doi：10.1186/s12864-015-1292-z）包含补充材料，可供授权用户使用。
Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with diseases of the colon including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). However, the functional role of many of these SNPs is largely unknown and tissue-specific resources are lacking. Expression quantitative trait loci (eQTL) mapping identifies target genes of disease-associated SNPs. This study provides a comprehensive eQTL map of distal colonic samples obtained from 40 healthy African Americans and demonstrates their relevance for GWAS of colonic diseases. 8.4 million imputed SNPs were tested for their associations with 16,252 expression probes representing 12,363 unique genes. 1,941 significant cis-eQTL, corresponding to 122 independent signals, were identified at a false discovery rate (FDR) of 0.01. Overall, among colon cis-eQTL, there was significant enrichment for GWAS variants for IBD (Crohn’s disease [CD] and ulcerative colitis [UC]) and CRC as well as type 2 diabetes and body mass index. ERAP2, ADCY3, INPP5E, UBA7, SFMBT1, NXPE1 and REXO2 were identified as target genes for IBD-associated variants. The CRC-associated eQTL rs3802842 was associated with the expression of C11orf93 (COLCA2). Enrichment of colon eQTL near transcription start sites and for active histone marks was demonstrated, and eQTL with high population differentiation were identified. Through the comprehensive study of eQTL in the human colon, this study identified novel target genes for IBD- and CRC-associated genetic variants. Moreover, bioinformatic characterization of colon eQTL provides a tissue-specific tool to improve understanding of biological differences in diseases between different ethnic groups. The online version of this article (doi:10.1186/s12864-015-1292-z) contains supplementary material, which is available to authorized users.
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影响因子：
4.5
作者：
Festen EA;Goyette P;Green T;Boucher G;Beauchamp C;Trynka G;Dubois PC;Lagacé C;Stokkers PC;Hommes DW;Barisani D;Palmieri O;Annese V;van Heel DA;Weersma RK;Daly MJ;Wijmenga C;Rioux JD
通讯作者：
Rioux JD
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：
30.8
作者：
通讯作者：
--
影响因子：
4.5
作者：
Brown CD;Mangravite LM;Engelhardt BE
通讯作者：
Engelhardt BE
影响因子：
30.8
作者：
Barrett, Jeffrey C.;Lee, James C.;Lees, Charles W.;Prescott, Natalie J.;Anderson, Carl A.;Phillips, Anne;Wesley, Emma;Parnell, Kirstie;Zhang, Hu;Drummond, Hazel;Nimmo, Elaine R.;Massey, Dunecan;Blaszczyk, Kasia;Elliott, Timothy;Cotterill, Lynn;Dallal, Helen;Lobo, Alan J.;Mowat, Craig;Sanderson, Jeremy D.;Jewell, Derek P.;Newman, William G.;Edwards, Cathryn;Ahmad, Tariq;Mansfield, John C.;Satsangi, Jack;Parkes, Miles;Mathew, Christopher G.;Donnelly, Peter;Peltonen, Leena;Blackwell, Jenefer M.;Bramon, Elvira;Brown, Matthew A.;Casas, Juan P.;Corvin, Aiden;Craddock, Nicholas;Deloukas, Panos;Duncanson, Audrey;Jankowski, Janusz;Markus, Hugh S.;McCarthy, Mark I.;Palmer, Colin N. A.;Plomin, Robert;Rautanen, Anna;Sawcer, Stephen J.;Samani, Nilesh;Trembath, Richard C.;Viswanathan, Ananth C.;Wood, Nicholas;Spencer, Chris C. A.;Bellenguez, Celine;Davison, Daniel;Freeman, Colin;Strange, Amy;Langford, Cordelia;Hunt, Sarah E.;Edkins, Sarah;Gwilliam, Rhian;Blackburn, Hannah;Bumpstead, Suzannah J.;Dronov, Serge;Gillman, Matthew;Gray, Emma;Hammond, Naomi;Jayakumar, Alagurevathi;McCann, Owen T.;Liddle, Jennifer;Perez, Marc L.;Potter, Simon C.;Ravindrarajah, Radhi;Ricketts, Michelle;Waller, Matthew;Weston, Paul;Widaa, Sara;Whittaker, Pamela;Attwood, Antony P.;Stephens, Jonathan;Sambrook, Jennifer;Ouwehand, Willem H.;McArdle, Wendy L.;Ring, Susan M.;Strachan, David P.
通讯作者：
Strachan, David P.