A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer.
A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer.
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DOI：
10.1038/srep10442
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发表时间：
2015-05-20
影响因子：
4.6
通讯作者：
Houlston RS
中科院分区：
文献类型：
--
作者：
Al-Tassan NA;Whiffin N;Hosking FJ;Palles C;Farrington SM;Dobbins SE;Harris R;Gorman M;Tenesa A;Meyer BF;Wakil SM;Kinnersley B;Campbell H;Martin L;Smith CG;Idziaszczyk S;Barclay E;Maughan TS;Kaplan R;Kerr R;Kerr D;Buchanan DD;Win AK;Hopper J;Jenkins M;Lindor NM;Newcomb PA;Gallinger S;Conti D;Schumacher F;Casey G;Dunlop MG;Tomlinson IP;Cheadle JP;Houlston RS
结直肠癌（CRC）的全基因组关联研究（GWAS）迄今已确定了23个易感基因座。对先前进行的GWAS的分析表明，尚未发现其他风险位点。为了确定新的CRC易感基因座，我们进行了一项新的GWAS，并对5个已发表的GWAS（总计7，577例病例和9，979例欧洲血统对照）进行了荟萃分析，利用1000个基因组计划估算基因型。联合分析确定了与1p36.2标记为rs72647484的CRC的新的显著相关性（次要等位基因频率[MAF] = 0.09）接近CDC 42和WNT 4（P = 1.21 × 10−8，比值比[OR] = 1.21），16q24.1标记为rs 16941835（MAF = 0.21，P = 5.06 × 10−8; OR = 1.15）在长非编码RNA（lncRNA）RP 11 - 58 A18.1内，距离最近的编码基因FOXL 1约500 kb。此外，我们发现在10 p13与rs 10904849内含子与CUBN有很好的关联（MAF = 0.32，P = 7.01 × 10-8; OR = 1.14）。这些发现为进一步了解CRC遗传易感性的遗传和生物学基础提供了依据。此外，我们的分析进一步表明，插补可用于利用GWAS数据来识别新的致病变异。
Genome-wide association studies (GWAS) of colorectal cancer (CRC) have identified 23 susceptibility loci thus far. Analyses of previously conducted GWAS indicate additional risk loci are yet to be discovered. To identify novel CRC susceptibility loci, we conducted a new GWAS and performed a meta-analysis with five published GWAS (totalling 7,577 cases and 9,979 controls of European ancestry), imputing genotypes utilising the 1000 Genomes Project. The combined analysis identified new, significant associations with CRC at 1p36.2 marked by rs72647484 (minor allele frequency [MAF] = 0.09) near CDC42 and WNT4 (P = 1.21 × 10−8, odds ratio [OR] = 1.21 ) and at 16q24.1 marked by rs16941835 (MAF = 0.21, P = 5.06 × 10−8; OR = 1.15) within the long non-coding RNA (lncRNA) RP11-58A18.1 and ~500 kb from the nearest coding gene FOXL1. Additionally we identified a promising association at 10p13 with rs10904849 intronic to CUBN (MAF = 0.32, P = 7.01 × 10-8; OR = 1.14). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CRC. Additionally, our analysis further demonstrates that imputation can be used to exploit GWAS data to identify novel disease-causing variants.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
2.8
作者：
Gao L;Bai L;Nan Qz
通讯作者：
Nan Qz
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：
Kircher, Martin;Witten, Daniela M.;Jain, Preti;O'Roak, Brian J.;Cooper, Gregory M.;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
11.5
作者：
Aaltonen, Lauri;Johns, Louise;Houlston, Richard
通讯作者：
Houlston, Richard