Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
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DOI：
10.1038/ng.2408
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发表时间：
2012-10
期刊：
影响因子：
30.8
通讯作者：
Wellcome Trust Case Control Consortium 2
中科院分区：
文献类型：
--
作者：
Su Z;Gay LJ;Strange A;Palles C;Band G;Whiteman DC;Lescai F;Langford C;Nanji M;Edkins S;van der Winkel A;Levine D;Sasieni P;Bellenguez C;Howarth K;Freeman C;Trudgill N;Tucker AT;Pirinen M;Peppelenbosch MP;van der Laan LJ;Kuipers EJ;Drenth JP;Peters WH;Reynolds JV;Kelleher DP;McManus R;Grabsch H;Prenen H;Bisschops R;Krishnadath K;Siersema PD;van Baal JW;Middleton M;Petty R;Gillies R;Burch N;Bhandari P;Paterson S;Edwards C;Penman I;Vaidya K;Ang Y;Murray I;Patel P;Ye W;Mullins P;Wu AH;Bird NC;Dallal H;Shaheen NJ;Murray LJ;Koss K;Bernstein L;Romero Y;Hardie LJ;Zhang R;Winter H;Corley DA;Panter S;Risch HA;Reid BJ;Sargeant I;Gammon MD;Smart H;Dhar A;McMurtry H;Ali H;Liu G;Casson AG;Chow WH;Rutter M;Tawil A;Morris D;Nwokolo C;Isaacs P;Rodgers C;Ragunath K;MacDonald C;Haigh C;Monk D;Davies G;Wajed S;Johnston D;Gibbons M;Cullen S;Church N;Langley R;Griffin M;Alderson D;Deloukas P;Hunt SE;Gray E;Dronov S;Potter SC;Tashakkori-Ghanbaria A;Anderson M;Brooks C;Blackwell JM;Bramon E;Brown MA;Casas JP;Corvin A;Duncanson A;Markus HS;Mathew CG;Palmer CN;Plomin R;Rautanen A;Sawcer SJ;Trembath RC;Viswanathan AC;Wood N;Trynka G;Wijmenga C;Cazier JB;Atherfold P;Nicholson AM;Gellatly NL;Glancy D;Cooper SC;Cunningham D;Lind T;Hapeshi J;Ferry D;Rathbone B;Brown J;Love S;Attwood S;MacGregor S;Watson P;Sanders S;Ek W;Harrison RF;Moayyedi P;de Caestecker J;Barr H;Stupka E;Vaughan TL;Peltonen L;Spencer CC;Tomlinson I;Donnelly P;Jankowski JA;Esophageal Adenocarcinoma Genetics Consortium;Wellcome Trust Case Control Consortium 2
巴雷特食管是一种越来越常见的疾病，与胃酸反流和裂孔疝密切相关。Barrett食管易患食管腺癌（EAC），这是一种预后很差的肿瘤。我们已经进行了Barrett食管的第一个全基因组关联研究，其中发现了1852例英国病例和5172例英国对照，复制了5986例病例和12825例对照。两个区域与疾病风险相关：染色体6p21， rs9257809 (Pcombined=4.09×10−9，OR（95%CI) =1.21(1.13-1.28)）和染色体16q24， rs9936833 (Pcombined=2.74×10−10，OR（95%CI) =1.14(1.10-1.19)）。6p21染色体上的顶端SNP位于主要组织相容性复合体内，16q24染色体上与rs9936833最近的蛋白编码基因是FOXF1，它与食道发育和结构有关。我们发现证据表明巴雷特食道的遗传成分是由许多小影响的常见变异介导的，易致肥胖的SNP等位基因也增加了巴雷特食道的风险。
Barrett’s Esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia. Barrett’s Esophagus strongly predisposes to esophageal adenocarcinoma (EAC), a tumour with a very poor prognosis. We have undertaken the first genome-wide association study on Barrett’s Esophagus, comprising 1,852 UK cases and 5,172 UK controls in discovery and 5,986 cases and 12,825 controls in the replication. Two regions were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10−9, OR(95%CI) =1.21(1.13-1.28)) and chromosome 16q24, rs9936833 (Pcombined=2.74×10−10, OR(95%CI) =1.14(1.10-1.19)). The top SNP on chromosome 6p21 is within the major histocompatibility complex, and the closest protein-coding gene to rs9936833 on chromosome 16q24 is FOXF1, which is implicated in esophageal development and structure. We found evidence that the genetic component of Barrett’s Esophagus is mediated by many common variants of small effect and that SNP alleles predisposing to obesity also increase risk for Barrett’s Esophagus.
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影响因子：
4.5
作者：
Heard-Costa NL;Zillikens MC;Monda KL;Johansson A;Harris TB;Fu M;Haritunians T;Feitosa MF;Aspelund T;Eiriksdottir G;Garcia M;Launer LJ;Smith AV;Mitchell BD;McArdle PF;Shuldiner AR;Bielinski SJ;Boerwinkle E;Brancati F;Demerath EW;Pankow JS;Arnold AM;Chen YD;Glazer NL;McKnight B;Psaty BM;Rotter JI;Amin N;Campbell H;Gyllensten U;Pattaro C;Pramstaller PP;Rudan I;Struchalin M;Vitart V;Gao X;Kraja A;Province MA;Zhang Q;Atwood LD;Dupuis J;Hirschhorn JN;Jaquish CE;O'Donnell CJ;Vasan RS;White CC;Aulchenko YS;Estrada K;Hofman A;Rivadeneira F;Uitterlinden AG;Witteman JC;Oostra BA;Kaplan RC;Gudnason V;O'Connell JR;Borecki IB;van Duijn CM;Cupples LA;Fox CS;North KE
通讯作者：
North KE
影响因子：
3.8
作者：
Chak, Amitabh;Ochs-Balcom, Heather;Eng, Charis
通讯作者：
Eng, Charis
影响因子：
45.3
作者：
Allum, William H.;Stenning, Sally P.;Langley, Ruth E.
通讯作者：
Langley, Ruth E.
影响因子：
7.6
作者：
Moayyedi, P.;Burch, N.;Jankowski, J.
通讯作者：
Jankowski, J.
影响因子：
4.5
作者：
Heid, Iris M.;Huth, Cornelia;Wichmann, H-Erich
通讯作者：
Wichmann, H-Erich