Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.
Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.
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DOI：
10.1038/ng.2616
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发表时间：
2013-06
期刊：
影响因子：
30.8
通讯作者：
Karlsen, Tom H.
中科院分区：
文献类型：
--
作者：
Liu, Jimmy Z.;Hov, Johannes Roksund;Folseraas, Trine;Ellinghaus, Eva;Rushbrook, Simon M.;Doncheva, Nadezhda T.;Andreassen, Ole A.;Weersma, Rinse K.;Weismueller, Tobias J.;Eksteen, Bertus;Invernizzi, Pietro;Hirschfield, Gideon M.;Gotthardt, Daniel Nils;Pares, Albert;Ellinghaus, David;Shah, Tejas;Juran, Brian D.;Milkiewicz, Piotr;Rust, Christian;Schramm, Christoph;Mueller, Tobias;Srivastava, Brijesh;Dalekos, Georgios;Noethen, Markus M.;Herms, Stefan;Winkelmann, Juliane;Mitrovic, Mitja;Braun, Felix;Ponsioen, Cyriel Y.;Croucher, Peter J. P.;Sterneck, Martina;Teufel, Andreas;Mason, Andrew L.;Saarela, Janna;Leppa, Virpi;Dorfman, Ruslan;Alvaro, Domenico;Floreani, Annarosa;Onengut-Gumuscu, Suna;Rich, Stephen S.;Thompson, Wesley K.;Schork, Andrew J.;Naess, Sigrid;Thomsen, Ingo;Mayr, Gabriele;Koenig, Inke R.;Hveem, Kristian;Cleynen, Isabelle;Gutierrez-Achury, Javier;Ricano-Ponce, Isis;van Heel, David;Bjoernsson, Einar;Sandford, Richard N.;Durie, Peter R.;Melum, Espen;Vatn, Morten H.;Silverberg, Mark S.;Duerr, Richard H.;Padyukov, Leonid;Brand, Stephan;Sans, Miquel;Annese, Vito;Achkar, Jean-Paul;Boberg, Kirsten Muri;Marschall, Hanns-Ulrich;Chazouilleres, Olivier;Bowlus, Christopher L.;Wijmenga, Cisca;Schrumpf, Erik;Vermeire, Severine;Albrecht, Mario;Rioux, John D.;Alexander, Graeme;Bergquist, Annika;Cho, Judy;Schreiber, Stefan;Manns, Michael P.;Farkkila, Martti;Dale, Anders M.;Chapman, Roger W.;Lazaridis, Konstantinos N.;Franke, Andre;Anderson, Carl A.;Karlsen, Tom H.
原发性硬化性胆管炎(PSC)是一种病因不明的严重肝病，导致胆管纤维性破坏，最终需要肝移植。我们比较了3,789例欧洲血统的PSC病例和25,079名对照人群，使用免疫芯片对130,422个SNP进行了基因分型。我们发现了12个人类白细胞抗原(HL A)复合体以外的全基因组显著关联，其中9个是新发现的，使已知的PSC风险基因座的数量增加到16个。尽管72%的病例与炎症性肠病(IBD)并存，但12个基因座中有6个与PSC的关联明显强于与IBD的关联，这表明这两种疾病的基因结构重叠但截然不同。我们在分析中结合了临床上发生的7种疾病的相关统计数据，发现了另外33个多效性PSC风险基因的提示性证据。结合网络分析，这些发现增加了PSC的遗传风险图，并扩大了PSC与其他免疫介导性疾病的关系。
Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation,,. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases.
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影响因子：
4.4
作者：
Kasler, Herbert G.;Young, Bryan D.;Verdin, Eric
通讯作者：
Verdin, Eric
影响因子：
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作者：
Broome, U;Olsson, R;Lindberg, G
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Lindberg, G
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Efron, Bradley
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作者：
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通讯作者：
Clayton, DG
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作者：
Folseraas, Trine;Melum, Espen;Rausch, Philipp;Juran, Brian D.;Ellinghaus, Eva;Shiryaev, Alexey;Laerdahl, Jon K.;Ellinghaus, David;Schramm, Christoph;Weismueller, Tobias J.;Gotthard, Daniel Nils;Hov, Johannes Roksund;Clausen, Ole Petter;Weersma, Rinse K.;Janse, Marcel;Boberg, Kirsten Muri;Bjornsson, Einar;Marschall, Hanns-Ulrich;Cleynen, Isabelle;Rosenstiel, Philip;Holm, Kristian;Teufel, Andreas;Rust, Christian;Gieger, Christian;Wichmann, H-Erich;Bergquist, Annika;Ryu, Euijung;Ponsioen, Cyriel Y.;Runz, Heiko;Sterneck, Martina;Vermeire, Severine;Beuers, Ulrich;Wijmenga, Cisca;Schrumpf, Erik;Manns, Michael P.;Lazaridis, Konstantinos N.;Schreiber, Stefan;Baines, John F.;Franke, Andre;Karlsen, Tom H.
通讯作者：
Karlsen, Tom H.