Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region.
Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region.
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DOI：
10.1038/ng.483
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发表时间：
2009-12
期刊：
影响因子：
30.8
通讯作者：
Strachan, David P.
中科院分区：
文献类型：
--
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.
溃疡性结肠炎(UC)是一种常见的炎症性肠病，病因复杂。作为惠康信托病例对照联合会2的一部分，我们对2361例病例和5417例对照进行了UC全基因组关联扫描。在2 321例病例和4 818名对照中，对P<；1×10−5处有关联的基因座进行了基因分型。我们发现在染色体20q13(HNF4a；P=3.2x10−17)、16q22(CDH1和CDH3；P=2.8×10−8)和7q31(Lamb1；3.0x10−8)上的三个新的基因座上存在显著的关联。值得注意的是，CDH1最近被认为与结直肠癌的易感性有关，结直肠癌是UC长期存在的一个公认的并发症。这些新的关联表明，肠上皮屏障完整性的改变可能有助于UC的发病。
Ulcerative colitis (UC) is a common form of inflammatory bowel disease with a complex aetiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome-wide association scan for UC in 2361 cases and 5417 controls. Loci showing evidence of association at P < 1 × 10−5 were followed up by genotyping in an independent set of 2321 cases and 4818 controls. We find genome-wide significant evidence of association at three new loci, each containing at least one biologically relevant candidate gene, on chromosomes 20q13 (HNF4A; P = 3.2 × 10−17), 16q22 (CDH1 and CDH3; P = 2.8 × 10−8) and 7q31 (LAMB1; 3.0 × 10−8). Of note, CDH1 has recently been associated with susceptibility to colorectal cancer, which is an established complication of longstanding UC. The new associations suggest that changes in the integrity of the intestinal epithelial barrier may contribute to the pathogenesis of UC.
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溃疡性结肠炎中克罗恩病风险的研究进一步定义了它们的分子关系。
影响因子：
29.4
作者：
Anderson CA;Massey DC;Barrett JC;Prescott NJ;Tremelling M;Fisher SA;Gwilliam R;Jacob J;Nimmo ER;Drummond H;Lees CW;Onnie CM;Hanson C;Blaszczyk K;Ravindrarajah R;Hunt S;Varma D;Hammond N;Lewis G;Attlesey H;Watkins N;Ouwehand W;Strachan D;McArdle W;Lewis CM;Wellcome Trust Case Control Consortium;Lobo A;Sanderson J;Jewell DP;Deloukas P;Mansfield JC;Mathew CG;Satsangi J;Parkes M
通讯作者：
Parkes M
影响因子：
7.6
作者：
Rubin, GP;Hungin, APS;Ling, J
通讯作者：
Ling, J
影响因子：
30.8
作者：
Fisher, Sheila A.;Tremelling, Mark;Anderson, Carl A.;Gwilliam, Rhian;Bumpstead, Suzannah;Prescott, Natalie J.;Nimmo, Elaine R.;Massey, Dunecan;Berzuini, Carlo;Johnson, Christopher;Barrett, Jeffrey C.;Cummings, Fraser R.;Drummond, Hazel;Lees, Charlie W.;Onnie, Clive M.;Hanson, Catherine E.;Blaszczyk, Katarzyna;Inouye, Mike;Ewels, Philip;Ravindrarajah, Radhi;Keniry, Andrew;Hunt, Sarah;Carter, Martyn;Watkins, Nick;Ouwehand, Willem;Lewis, Cathryn M.;Cardon, Lon;Lobo, Alan;Forbes, Alastair;Sanderson, Jeremy;Jewell, Derek P.;Mansfield, John C.;Deloukas, Panos;Mathew, Christopher G.;Parkes, Miles;Satsangi, Jack
通讯作者：
Satsangi, Jack
影响因子：
30.8
作者：
通讯作者：
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影响因子：
30.8
作者：
Kugathasan, Subra;Baldassano, Robert N.;Bradfield, Jonathan P.;Sleiman, Patrick M. A.;Imielinski, Marcin;Guthery, Stephen L.;Cucchiara, Salvatore;Kim, Cecilia E.;Frackelton, Edward C.;Annaiah, Kiran;Glessner, Joseph T.;Santa, Erin;Willson, Tara;Eckert, Andrew W.;Bonkowski, Erin;Shaner, Julie L.;Smith, Ryan M.;Otieno, F. George;Peterson, Nicholas;Abrams, Debra J.;Chiavacci, Rosetta M.;Grundmeier, Robert;Mamula, Petar;Tomer, Gitit;Piccoli, David A.;Monos, Dimitri S.;Annese, Vito;Denson, Lee A.;Grant, Struan F. A.;Hakonarson, Hakon
通讯作者：
Hakonarson, Hakon