title: Genome-wide association study identifies new susceptibility loci for cutaneous lupus erythematosus.
abstract: Cutaneous lupus erythematosus (CLE) is a chronic autoimmune disease of the skin with typical clinical manifestations. Here, we genotyped 906 600 single nucleotide polymorphisms (SNPs) in 183 CLE cases and 1288 controls of Central European ancestry. Replication was performed for 13 SNPs in 219 case subjects and 262 controls from Finland. Association was particularly pronounced at 4 loci, all with genomewide significance (P < 5 × 10(-8) ): rs2187668 (PGWAS  = 1.4 × 10(-12) ), rs9267531 (PGWAS  = 4.7 × 10(-10) ), rs4410767 (PGWAS  = 1.0 × 10(-9) ) and rs3094084 (PGWAS  = 1.1 × 10(-9) ). All mentioned SNPs are located within the major histocompatibility complex (MHC) region of chromosome 6 and near genes of known immune functions or associations with other autoimmune diseases such as HLA-DQ alpha chain 1 (HLA-DQA1), MICA, MICB, MSH5, TRIM39 and RPP21. For example, TRIM39/RPP21 read through transcript is a known mediator of the interferon response, a central pathway involved in the pathogenesis of CLE and systemic lupus erythematosus (SLE). Taken together, this genomewide analysis of disease association of CLE identified candidate genes and genomic regions that may contribute to pathogenic mechanisms in CLE via dysregulated antigen presentation (HLA-DQA1), apoptosis regulation, RNA processing and interferon response (MICA, MICB, MSH5, TRIM39 and RPP21).
authors.affiliation: Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kunz
authors.affiliation: Institut für Medizinische Biometrie und Statistik, und Zentrum für Klinische Studien, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany.
authors.forename: Inke R
authors.initials: IR
authors.lastname: König
authors.affiliation: Institut für Medizinische Biometrie und Statistik, und Zentrum für Klinische Studien, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Schillert
authors.affiliation: Institut für Medizinische Biometrie und Statistik, und Zentrum für Klinische Studien, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Kruppa
authors.affiliation: Institut für Medizinische Biometrie und Statistik, und Zentrum für Klinische Studien, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.affiliation: Research unit of Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Diabetes Research, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.affiliation: Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|Department of Medicine I, Ludwig Maximilian University Munich, Munich, Germany.|German Center for Cardiovascular Research, Munich Heart Alliance, Munich, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Müller-Nurasyid
authors.affiliation: Institute for Epidemiology and Biobank popgen, Christian-Albrechts-University of Kiel, Kiel, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.affiliation: Department of Dermatology and Allergology, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Annamari
authors.initials: A
authors.lastname: Ranki
authors.affiliation: Department of Dermatology and Allergology, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Panelius
authors.affiliation: Department of Dermatology and Allergology, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Koskenmies
authors.affiliation: Department of Dermatology, Tampere University Central Hospital, University of Tampere, Tampere, Finland.
authors.forename: Taina
authors.initials: T
authors.lastname: Hasan
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden.|Department of Medical Genetics, Folkhälsan Institute of Genetics, University of Helsinki, Helsinki, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.affiliation: Clinical Research Center, Karolinska University Hospital, Huddinge, Sweden.
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Rönn
authors.affiliation: Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Simon
authors.affiliation: Department of Dermatology, Allergology and Venereology, University of Schleswig-Holstein, Lübeck, Germany.
authors.forename: Enno
authors.initials: E
authors.lastname: Schmidt
authors.affiliation: Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Wenzel
authors.affiliation: Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tüting
authors.affiliation: Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Landsberg
authors.affiliation: University Heart Center Hamburg, Clinic for General and Interventional Cardiology, German Center for Cardiovascular Research (DZHK), Hamburg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.affiliation: University Heart Center Hamburg, Clinic for General and Interventional Cardiology, German Center for Cardiovascular Research (DZHK), Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.affiliation: Department of Dermatology and Allergology, University of Schleswig-Holstein, Kiel, Germany.
authors.forename: Regine
authors.initials: R
authors.lastname: Gläser
authors.affiliation: Department of Dermatology, Venereology and Allergology, Ruhr-University of Bochum, Bochum, Germany.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Patsinakidis
authors.affiliation: Division of Immunogenetics, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Annegret
authors.initials: A
authors.lastname: Kuhn
authors.affiliation: Department of Dermatology, Allergology and Venereology, University of Schleswig-Holstein, Lübeck, Germany.
authors.forename: Saleh M
authors.initials: SM
authors.lastname: Ibrahim
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005387:Finland; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005858:Germany; D059848:HLA-DQ alpha-Chains / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008178:Lupus Erythematosus, Cutaneous / Q000235:genetics* / Q000276:immunology; D008285:Major Histocompatibility Complex; D020641:Polymorphism, Single Nucleotide; D043262:Ribonuclease P / Q000235:genetics; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C098080:MICB antigen; C118481:MSH5 protein, human; C414583:TRIM39 protein, human; D044767:Ubiquitin-Protein Ligases; D043262:Ribonuclease P
keywords: autoimmune diseases; genetics; lupus; single nucleotide polymorphisms