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Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture.
Stuart, Philip E; Nair, Rajan P; Tsoi, Lam C; Tejasvi, Trilokraj; Das, Sayantan; Kang, Hyun Min; Ellinghaus, Eva; Chandran, Vinod; Callis-Duffin, Kristina; Ike, Robert; Li, Yanming; Wen, Xiaoquan; Enerbäck, Charlotta; Gudjonsson, Johann E; Kõks, Sulev; Kingo, Külli; Esko, Tõnu; Mrowietz, Ulrich; Reis, Andre; Wichmann, H Erich; Gieger, Christian; Hoffmann, Per; Nöthen, Markus M; Winkelmann, Juliane; Kunz, Manfred; Moreta, Elvia G; Mease, Philip J; Ritchlin, Christopher T; Bowcock, Anne M; Krueger, Gerald G; Lim, Henry W; Weidinger, Stephan; Weichenthal, Michael; Voorhees, John J; Rahman, Proton; Gregersen, Peter K; Franke, Andre; Gladman, Dafna D; Abecasis, Gonçalo R; Elder, James T.
Afiliação
  • Stuart PE; Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Nair RP; Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Tsoi LC; Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 4
  • Tejasvi T; Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Ann Arbor Veterans Affairs Hospital, Ann Arbor, MI 48105, USA.
  • Das S; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Kang HM; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Ellinghaus E; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany.
  • Chandran V; Department of Medicine, Division of Rheumatology, University of Toronto, Toronto, ON M5T 2S8, Canada; Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Research Institute, University of Toronto, Toronto, ON M5T 2S8, Canada.
  • Callis-Duffin K; Department of Dermatology, University of Utah, Salt Lake City, UT 84132, USA.
  • Ike R; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Li Y; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Wen X; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Enerbäck C; Department of Clinical and Experimental Medicine, Division of Cell Biology and Dermatology, Linköping University, 581 83 Linköping, Sweden.
  • Gudjonsson JE; Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Kõks S; Department of Pathophysiology, Centre of Translational Medicine and Centre for Translational Genomics, University of Tartu, 50411 Tartu, Estonia; Department of Reproductive Biology, Estonian University of Life Sciences, 51014 Tartu, Estonia.
  • Kingo K; Dermatology Clinic, Tartu University Hospital, Department of Dermatology and Venereology, University of Tartu, 50417 Tartu, Estonia.
  • Esko T; Estonian Genome Center, University of Tartu, 51010 Tartu, Estonia.
  • Mrowietz U; Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
  • Reis A; Institute of Human Genetics, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
  • Wichmann HE; Institute of Epidemiology I, Helmholtz Zentrum Munich, German Research Center for Environmental Health, 85764 Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, 81377 Munich, Germany; Institute of Medical Statistics and Epidemiology, Tech
  • Gieger C; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  • Hoffmann P; Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, 53127 Bonn, Germany.
  • Nöthen MM; Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, 53127 Bonn, Germany.
  • Winkelmann J; Neurologische Klinik and Poliklinik, Klinikum rechts der Isar, Technische Universität München, 80333 Munich, Germany; Institute of Neurogenomics, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  • Kunz M; Department of Dermatology, Venereology and Allergology, University of Leipzig, 04103 Leipzig, Germany.
  • Moreta EG; Saint Paul Rheumatology, Eagan, MN 55121, USA.
  • Mease PJ; Seattle Rheumatology Associates, 601 Broadway, Suite 600, Seattle, WA 98122, USA.
  • Ritchlin CT; Allergy, Immunology, and Rheumatology Division, University of Rochester Medical Center, Rochester, NY 14623, USA.
  • Bowcock AM; National Heart and Lung Institute, Imperial College, London SW7 2AZ, UK.
  • Krueger GG; Department of Dermatology, University of Utah, Salt Lake City, UT 84132, USA.
  • Lim HW; Department of Dermatology, Henry Ford Hospital, Detroit, MI 48202, USA.
  • Weidinger S; Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
  • Weichenthal M; Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
  • Voorhees JJ; Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Rahman P; Memorial University, St. John's, NL A1C 5B8, Canada.
  • Gregersen PK; The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY 11030, USA.
  • Franke A; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany.
  • Gladman DD; Department of Medicine, Division of Rheumatology, University of Toronto, Toronto, ON M5T 2S8, Canada; Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Research Institute, University of Toronto, Toronto, ON M5T 2S8, Canada.
  • Abecasis GR; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Elder JT; Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Ann Arbor Veterans Affairs Hospital, Ann Arbor, MI 48105, USA. Electronic address: jelder@umich.edu.
Am J Hum Genet ; 97(6): 816-36, 2015 Dec 03.
Article em En | MEDLINE | ID: mdl-26626624
ABSTRACT
Psoriasis vulgaris (PsV) is a common inflammatory and hyperproliferative skin disease. Up to 30% of people with PsV eventually develop psoriatic arthritis (PsA), an inflammatory musculoskeletal condition. To discern differences in genetic risk factors for PsA and cutaneous-only psoriasis (PsC), we carried out a genome-wide association study (GWAS) of 1,430 PsA case subjects and 1,417 unaffected control subjects. Meta-analysis of this study with three other GWASs and two targeted genotyping studies, encompassing a total of 9,293 PsV case subjects, 3,061 PsA case subjects, 3,110 PsC case subjects, and 13,670 unaffected control subjects of European descent, detected 10 regions associated with PsA and 11 with PsC at genome-wide (GW) significance. Several of these association signals (IFNLR1, IFIH1, NFKBIA for PsA; TNFRSF9, LCE3C/B, TRAF3IP2, IL23A, NFKBIA for PsC) have not previously achieved GW significance. After replication, we also identified a PsV-associated SNP near CDKAL1 (rs4712528, odds ratio [OR] = 1.16, p = 8.4 × 10(-11)). Among identified psoriasis risk variants, three were more strongly associated with PsC than PsA (rs12189871 near HLA-C, p = 5.0 × 10(-19); rs4908742 near TNFRSF9, p = 0.00020; rs10888503 near LCE3A, p = 0.0014), and two were more strongly associated with PsA than PsC (rs12044149 near IL23R, p = 0.00018; rs9321623 near TNFAIP3, p = 0.00022). The PsA-specific variants were independent of previously identified psoriasis variants near IL23R and TNFAIP3. We also found multiple independent susceptibility variants in the IL12B, NOS2, and IFIH1 regions. These results provide insights into the pathogenetic similarities and differences between PsC and PsA.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Psoríase / Artrite Psoriásica / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Loci Gênicos Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adolescent / Adult / Female / Humans / Male Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Psoríase / Artrite Psoriásica / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Loci Gênicos Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adolescent / Adult / Female / Humans / Male Idioma: En Ano de publicação: 2015 Tipo de documento: Article