Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis
| Autor: | Carl A. Anderson, Konstantinos N. Lazaridis, Isabelle Cleynen, Wesley K. Thompson, Ole A. Andreassen, Andreas Teufel, Felix Braun, Einar Björnsson, John D. Rioux, Roger W. Chapman, Inke R. König, Javier Gutierrez-Achury, Gabriele Mayr, Stefan Schreiber, Stephan Brand, Mitja Mitrovic, Annika Bergquist, Michael P. Manns, Jean-Paul Achkar, Simon M. Rushbrook, Cyriel Y. Ponsioen, Martina Sterneck, Kirsten Muri Boberg, Christian Rust, Andrew J. Schork, Albert Parés, Gideon M. Hirschfield, Graeme J.M. Alexander, Espen Melum, Bertus Eksteen, Juliane Winkelmann, Cisca Wijmenga, Ingo Thomsen, Hanns-Ulrich Marschall, Isis Ricaño-Ponce, Erik Schrumpf, Peter J. P. Croucher, Jimmy Z. Liu, Richard H. Duerr, Nadezhda Tsankova Doncheva, Annarosa Floreani, Eva Ellinghaus, Markus M. Nöthen, Brian D. Juran, Judy H. Cho, Mario Albrecht, Stefan Herms, Tobias J. Weismüller, Leonid Padyukov, Virpi Leppa, Morten H. Vatn, Mark S. Silverberg, Tobias Müller, Olivier Chazouillères, Domenico Alvaro, Christoph Schramm, Ruslan Dorfman, Richard Sandford, David A. van Heel, Rinse K. Weersma, Suna Onengut-Gumuscu, Anders M. Dale, Martti Färkkilä, Brijesh Srivastava, Severine Vermeire, Trine Folseraas, Vito Annese, Pietro Invernizzi, Tejas Shah, Daniel Gotthardt, Janna Saarela, Christopher L. Bowlus, Sigrid Næss, Andrew Mason, Stephen S. Rich, Johannes R. Hov, Peter R. Durie, Andre Franke, Kristian Hveem, Tom H. Karlsen, Piotr Milkiewicz, Miquel Sans, Georgios N. Dalekos, David Ellinghaus |
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| Přispěvatelé: | Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Wellcome Trust Sanger Inst, Cambridge, England, Oslo Univ Hosp, Rikshosp, Div Canc Med Surg & Transplantat, Norwegian PSC Res Ctr,Dept Transplantat Med, Oslo, Norway Oslo Univ Hosp, Rikshosp, Internal Med Res Inst, KG Jebsen Inflammat Res Ctr, Oslo, Norway Univ Oslo, Inst Clin Med, Oslo, Norway Oslo Univ Hosp, Rikshosp, Div Canc Med Surg & Transplantat, Sect Gastroenterol,Dept Transplantat Med, Oslo, Norway Univ Kiel, Inst Clin Mol Biol, Kiel, Germany Dept Gastroenterol & Hepatol, Norfolk, VA USA Univ Hosp Natl Hlth Serv NHS Trust, Norwich, Norfolk, England Max Planck Inst Informat, D-66123 Saarbrucken, Germany Oslo Univ Hosp, Div Mental Hlth & Addict, KG Jebsen Ctr Psychosis Res, Oslo, Norway Univ Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany Hannover Med Sch, Integrated Res & Treatment Ctr Transplantat IFB T, Hannover, Germany Univ Calgary, Dept Med, Snyder Inst Chron Dis, Calgary, AB, Canada Humanitas Clin & Res Ctr, Ctr Autoimmune Liver Dis, Rozzano, Italy Univ Toronto, Dept Med, Div Gastroenterol, Toronto, ON, Canada NIHR, Liver Res Ctr, Biomed Res Unit, Birmingham, W Midlands, England Univ Heidelberg Hosp, Dept Med, Heidelberg, Germany Univ Barcelona, IDIBAPS, CIBERehd, Liver Unit,Hosp Clin, Barcelona, Spain Mayo Clin, Coll Med, Ctr Basic Res Digest Dis, Div Gastroenterol & Hepatol, Rochester, MN USA Pomeranian Med Univ, Liver Unit, Szczecin, Poland Pomeranian Med Univ, Liver Res Labs, Szczecin, Poland Univ Munich, Dept Med 2, Munich, Germany Univ Med Ctr Hamburg Eppendorf, Dept Med 1, Hamburg, Germany Charite, Dept Internal Med Hepatol & Gastroenterol, D-13353 Berlin, Germany Univ Cambridge, Acad Dept Med Genet, Cambridge, England Univ Thessaly, Sch Med, Dept Med, Larisa, Greece Univ Thessaly, Sch Med, Larisa, Greece Univ Bonn, Inst Human Genet, Bonn, Germany Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany Tech Univ Munich, Dept Neurol, D-80290 Munich, Germany German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany Univ Groningen, Dept Genet, Groningen, Netherlands Univ Med Ctr Schleswig Holstein, Dept Gen Visceral Thorac Transplantat & Pediat Su, Kiel, Germany Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, NL-1105 AZ Amsterdam, Netherlands Univ Calif Berkeley, Dept Environm Sci Policy & Management, Berkeley, CA 94720 USA Univ Med Ctr Hamburg Eppendorf, Dept Hepatobiliary Surg & Transplantat, Hamburg, Germany Johannes Gutenberg Univ Mainz, Dept Med 1, Mainz, Germany Univ Alberta, Div Gastroenterol & Hepatol, Edmonton, AB, Canada Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland Univ Helsinki, FIMM, Publ Hlth Genom Unit, Helsinki, Finland Natl Inst Hlth & Welf, Helsinki, Finland Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada Univ Roma La Sapienza, Dept Clin Med, Div Gastroenterol, Rome, Italy Univ Padua, Dept Surg Oncol & Gastroenterol Sci, Padua, Italy Univ Virginia, Div Endocrinol & Metab, Ctr Publ Hlth Genom, Charlottesville, VA USA Univ Virginia, Dept Internal Med, Div Endocrinol & Metab, Charlottesville, VA USA Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA Univ Calif San Diego, Grad Program Cognit Sci, La Jolla, CA 92093 USA Med Univ Lubeck, Inst Med Biometry & Stat, D-23538 Lubeck, Germany Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth, N-7034 Trondheim, Norway Katholieke Univ Leuven, Dept Clin & Expt Med, Louvain, Belgium Queen Mary Univ London, Blizard Inst, Barts & London Sch Med & Dent, London, England Landspitali Univ Hosp, Dept Internal Med, Div Gastroenterol & Hepatol, Reykjavik, Iceland Hosp Sick Children, Physiol & Expt Med Res Inst, Toronto, ON M5G 1X8, Canada Akershus Univ Hosp, EpiGen, Nordbyhagen, Norway Mt Sinai Hosp, Inflammatory Bowel Dis IBD Grp, Zane Cohen Ctr Digest Dis, Toronto, ON M5G 1X5, Canada Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden Karolinska Univ Hosp Solna, Stockholm, Sweden Univ Munich, Univ Hosp Munich Grosshadern, Dept Med 2, Munich, Germany Ctr Med Teknon, Dept Digest Dis, Barcelona, Spain Casa Sollievodella Sofferenza Hosp, Ist Ricovero & Cura Carattere Sci, Div Gastroenterol, San Giovanni Rotondo, Italy Azienda Osped Univ Careggi, Unit Gastroenterol SOD2, Florence, Italy Cleveland Clin, Dept Gastroenterol & Hepatol, Inst Digest Dis, Cleveland, OH 44106 USA Cleveland Clin, Lerner Res Inst, Dept Pathobiol, Cleveland, OH 44106 USA Sahlgrens Acad, Inst Med, Dept Internal Med, Gothenburg, Sweden Univ Hosp, Gothenburg, Sweden Univ Paris 06, Hop St Antoine, AP HP, Dept Hepatol, Paris, France Univ Calif Davis, Div Gastroenterol & Hepatol, Davis, CA 95616 USA Katholieke Univ Leuven Hosp, Dept Gastroenterol, Louvain, Belgium Univ Med Greifswald, Dept Bioinformat, Inst Biometr & Med Informat, Greifswald, Germany Univ Montreal, Res Ctr, Montreal, PQ, Canada Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada Univ Cambridge, Dept Med, Div Hepatol, Cambridge CB2 2QQ, England Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Gastroenterol & Hepatol, Stockholm, Sweden Yale Univ, Dept Med, Sect Digest Dis, New Haven, CT 06520 USA Univ Kiel, Dept Gen Internal Med, Kiel, Germany Univ Kiel, Univ Hosp Schleswig Holstein, PopGen Biobank, Kiel, Germany Helsinki Univ Hosp, Dept Med, Div Gastroenterol, Helsinki, Finland Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA John Radcliffe Univ Hosp NHS Trust, Dept Hepatol, Oxford, England Univ Bergen, Dept Clin Med, Div Gastroenterol, Bergen, Norway, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Linkage disequilibrium
HISTONE DEACETYLASE Genotyping Techniques endocrine system diseases Genome-wide association study Disease Bioinformatics Linkage Disequilibrium 0302 clinical medicine Gene Frequency Risk Factors Oligonucleotide Array Sequence Analysis 0303 health sciences Crohn's disease education.field_of_study digestive oral and skin physiology CELIAC-DISEASE Genetic Pleiotropy Lifrarsjúkdómar 3. Good health FALSE DISCOVERY RATE ULCERATIVE-COLITIS genetic association study disease genetics 030211 gastroenterology & hepatology SUSCEPTIBILITY LOCI Population Cholangitis Sclerosing Single-nucleotide polymorphism Human leukocyte antigen GENETIC RISK Biology liver Polymorphism Single Nucleotide digestive system Article Primary sclerosing cholangitis 03 medical and health sciences FUNCTIONAL SIMILARITY Genetics medicine Humans GENOME-WIDE ASSOCIATION education 030304 developmental biology NATURAL-HISTORY Arfgengi medicine.disease digestive system diseases immunogenetics Genetic Loci Case-Control Studies Immunology Genome-Wide Association Study INFLAMMATORY-BOWEL-DISEASE |
| Zdroj: | Liu, JZ; Hov, JR; Folseraas, T; Ellinghaus, E; Rushbrook, SM; Doncheva, NT; et al.(2013). Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis. Nature Genetics, 45(6), 670-675. doi: 10.1038/ng.2616. UC Davis: Retrieved from: http://www.escholarship.org/uc/item/3dv430kz Nature Genetics, 45(6), 670-675. Nature Publishing Group Liu, J Z, Hov, J R, Folseraas, T, Ellinghaus, E, Rushbrook, S M, Doncheva, N T, Andreassen, O A, Weersma, R K, Weismüller, T J, Eksteen, B, Invernizzi, P, Hirschfield, G M, Gotthardt, D N, Pares, A, Ellinghaus, D, Shah, T, Juran, B D, Milkiewicz, P, Rust, C, Schramm, C, Müller, T, Srivastava, B, Dalekos, G, Nöthen, M M, Herms, S, Winkelmann, J, Mitrovic, M, Braun, F, Ponsioen, C Y, Croucher, P J P, Sterneck, M, Teufel, A, Mason, A L, Saarela, J, Leppa, V, Dorfman, R, Alvaro, D, Floreani, A, Onengut-Gumuscu, S, Rich, S S, Thompson, W K, Schork, A J, Næss, S, Thomsen, I, Mayr, G, König, I R, Hveem, K, Cleynen, I, Gutierrez-Achury, J, Ricaño-Ponce, I & UK-PSCSC Consortium 2013, ' Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis ', Nature Genetics, vol. 45, no. 6, pp. 670-675 . https://doi.org/10.1038/ng.2616 Nature genetics Nature genetics, 45(6), 670-675. Nature Publishing Group Nature Genetics |
| ISSN: | 1061-4036 |
| Popis: | To access publisher's full text version of this article click on the hyperlink at the bottom of the page 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. Norwegian PSC Research Center German Ministry of Education and Research through the National Genome Research Network 01GS0809-GP7 Deutsche Forschungsgemeinschaft FR 2821/2-1 Integrated Research and Treatment Center-Transplantation 01EO0802 PopGen Biobank Wellcome Trust 098051 info:eu-repo/grantAgreement/EC/FP7/262055 |
| Databáze: | OpenAIRE |
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