Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease.
Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease.
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2q35（PNKD和TMBIM1）的变化影响结直肠癌的风险，并鉴定出与炎症性肠病的多效效应。
DOI：
10.1093/hmg/ddw087
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发表时间：
2016-06-01
影响因子：
3.5
通讯作者：
Houlston RS
中科院分区：
文献类型：
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作者：
Orlando G;Law PJ;Palin K;Tuupanen S;Gylfe A;Hänninen UA;Cajuso T;Tanskanen T;Kondelin J;Kaasinen E;Sarin AP;Kaprio J;Eriksson JG;Rissanen H;Knekt P;Pukkala E;Jousilahti P;Salomaa V;Ripatti S;Palotie A;Järvinen H;Renkonen-Sinisalo L;Lepistö A;Böhm J;Mecklin JP;Al-Tassan NA;Palles C;Martin L;Barclay E;Tenesa A;Farrington S;Timofeeva MN;Meyer BF;Wakil SM;Campbell H;Smith CG;Idziaszczyk S;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;Taipale J;Cheadle JP;Dunlop MG;Tomlinson IP;Aaltonen LA;Houlston RS
为了确定结直肠癌（CRC）的新风险位点，我们对7项独立重复的全基因组关联研究（GWAS）进行了荟萃分析，共有13656例CRC病例和21667例欧洲血统对照。联合分析确定了2 q35处CRC的新风险关联，标记为rs 992157（P = 3.15 × 10−8，比值比= 1.10，95%置信区间= 1.06-1.13），与PNKD（阵发性非运动诱发性运动障碍）和TMBIM 1（含1的跨膜BAX抑制剂基序）是内含子。有趣的是，这种易感性单核苷酸多态性（SNP）与先前发现的炎症性肠病（IBD）的GWAS SNP rs 2382817处于强连锁不平衡（r2 = 0.90，D′ = 0.96）。根据这一观察结果，我们检查了CRC和200个已建立的IBD风险基因座之间的多效性或共享遗传易感性，确定了另外11个显著关联（错误发现率[FDR]< 0.05）。我们的研究结果提供了进一步深入了解CRC遗传易感性的生物学基础，并确定了可能影响CRC和IBD发展的风险因素。
To identify new risk loci for colorectal cancer (CRC), we conducted a meta-analysis of seven genome-wide association studies (GWAS) with independent replication, totalling 13 656 CRC cases and 21 667 controls of European ancestry. The combined analysis identified a new risk association for CRC at 2q35 marked by rs992157 (P = 3.15 × 10−8, odds ratio = 1.10, 95% confidence interval = 1.06–1.13), which is intronic to PNKD (paroxysmal non-kinesigenic dyskinesia) and TMBIM1 (transmembrane BAX inhibitor motif containing 1). Intriguingly this susceptibility single-nucleotide polymorphism (SNP) is in strong linkage disequilibrium (r2 = 0.90, D′ = 0.96) with the previously discovered GWAS SNP rs2382817 for inflammatory bowel disease (IBD). Following on from this observation we examined for pleiotropy, or shared genetic susceptibility, between CRC and the 200 established IBD risk loci, identifying an additional 11 significant associations (false discovery rate [FDR]) < 0.05). Our findings provide further insight into the biological basis of inherited genetic susceptibility to CRC, and identify risk factors that may influence the development of both CRC and IBD.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
14.9
作者：
Chatr-Aryamontri A;Breitkreutz BJ;Heinicke S;Boucher L;Winter A;Stark C;Nixon J;Ramage L;Kolas N;O'Donnell L;Reguly T;Breitkreutz A;Sellam A;Chen D;Chang C;Rust J;Livstone M;Oughtred R;Dolinski K;Tyers M
通讯作者：
Tyers M
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
29.4
作者：
Costea, Irina;Mack, David R.;Amre, Devendra K.
通讯作者：
Amre, Devendra K.
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