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Psoriasis: HELP
Articles by Stephan Weidinger
Based on 21 articles published since 2010
(Why 21 articles?)
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Between 2010 and 2020, S. Weidinger wrote the following 21 articles about Psoriasis.
 
+ Citations + Abstracts
1 Article Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients. 2018

Patrick, Matthew T / Stuart, Philip E / Raja, Kalpana / Gudjonsson, Johann E / Tejasvi, Trilokraj / Yang, Jingjing / Chandran, Vinod / Das, Sayantan / Callis-Duffin, Kristina / Ellinghaus, Eva / Enerbäck, Charlotta / Esko, Tõnu / Franke, Andre / Kang, Hyun M / Krueger, Gerald G / Lim, Henry W / Rahman, Proton / Rosen, Cheryl F / Weidinger, Stephan / Weichenthal, Michael / Wen, Xiaoquan / Voorhees, John J / Abecasis, Gonçalo R / Gladman, Dafna D / Nair, Rajan P / Elder, James T / Tsoi, Lam C. ·Department of Dermatology, University of Michigan Medical School, Ann Arbor, 48109, MI, USA. · Morgridge Institute for Research, Madison, 53715, WI, USA. · Ann Arbor Veterans Affairs Hospital, Ann Arbor, 48105, MI, USA. · Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA. · Department of Human Genetics, Emory University School of Medicine, Atlanta, 30322, GA, USA. · Department of Medicine, Division of Rheumatology, University of Toronto, Toronto, Ontario, M5G 2C4, Canada. · Centre for Prognosis Studies in the Rheumatic Diseases, Krembil Research Institute, University of Toronto, Toronto, Ontario, M5T 2S8, Canada. · Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. · Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. · Department of Dermatology, University of Utah, Salt Lake City, Utah, 84132, USA. · Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, 24105, Germany. · Department of Dermatology, Linköping University, Linköping, SE-581 83, Sweden. · Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia. · Broad Institute of MIT and Harvard, Cambridge, Massachusetts, 02142, USA. · Department of Dermatology, Henry Ford Hospital, Detroit, 48202, MI, USA. · Memorial University, St. John's, Newfoundland and Labrador, A1B 3X9, Canada. · Division of Dermatology, Toronto Western Hospital, University of Toronto, Toronto, M5G 2C4, Ontario, Canada. · Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, 24105, Germany. · Department of Dermatology, University of Michigan Medical School, Ann Arbor, 48109, MI, USA. alextsoi@med.umich.edu. · Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA. alextsoi@med.umich.edu. · Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, 4810, MI, USA. alextsoi@med.umich.edu. ·Nat Commun · Pubmed #30301895.

ABSTRACT: Psoriatic arthritis (PsA) is a complex chronic musculoskeletal condition that occurs in ~30% of psoriasis patients. Currently, no systematic strategy is available that utilizes the differences in genetic architecture between PsA and cutaneous-only psoriasis (PsC) to assess PsA risk before symptoms appear. Here, we introduce a computational pipeline for predicting PsA among psoriasis patients using data from six cohorts with >7000 genotyped PsA and PsC patients. We identify 9 new loci for psoriasis or its subtypes and achieve 0.82 area under the receiver operator curve in distinguishing PsA vs. PsC when using 200 genetic markers. Among the top 5% of our PsA prediction we achieve >90% precision with 100% specificity and 16% recall for predicting PsA among psoriatic patients, using conditional inference forest or shrinkage discriminant analysis. Combining statistical and machine-learning techniques, we show that the underlying genetic differences between psoriasis subtypes can be used for individualized subtype risk assessment.

2 Article Meta-analysis of RNA sequencing datasets reveals an association between TRAJ23, psoriasis, and IL-17A. 2018

Merleev, Alexander A / Marusina, Alina I / Ma, Chelsea / Elder, James T / Tsoi, Lam C / Raychaudhuri, Siba P / Weidinger, Stephan / Wang, Elizabeth A / Adamopoulos, Iannis E / Luxardi, Guillaume / Gudjonsson, Johann E / Shimoda, Michiko / Maverakis, Emanual. ·Department of Dermatology, School of Medicine, UCD, Sacramento, California, USA. · Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA. · Department of Internal Medicine, Division of Rheumatology, Allergy & Clinical immunology, UCD School of Medicine, Sacramento, California, USA. · VA Medical Center Sacramento, Division of Rheumatology & Immunology, Sacramento, California, USA. · Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany. · Department of Medical Microbiology and Immunology, School of Medicine, UCD, California, USA. ·JCI Insight · Pubmed #29997305.

ABSTRACT: Numerous studies of relatively few patients have linked T cell receptor (TCR) genes to psoriasis but have yielded dramatically conflicting results. To resolve these discrepancies, we have chosen to mine RNA-Seq datasets for patterns of TCR gene segment usage in psoriasis. A meta-analysis of 3 existing and 1 unpublished datasets revealed a statistically significant link between the relative expression of TRAJ23 and psoriasis and the psoriasis-associated cytokine IL-17A. TRGV5, a TCR-γ segment, was also associated with psoriasis but correlated instead with IL-36A, other IL-36 family members, and IL-17C (not IL-17A). In contrast, TRAJ39 was strongly associated with healthy skin. T cell diversity measurements and analysis of CDR3 sequences were also conducted, revealing no psoriasis-associated public CDR3 sequences. Finally, in comparison with the expression of TCR-αβ genes, the expression of TCR-γδ genes was relatively low but mildly elevated in psoriatic skin. These results have implications for the development of targeted therapies for psoriasis and other autoimmune diseases. Also, the techniques employed in this study have applications in other fields, such as cancer immunology and infectious disease.

3 Article Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling. 2017

Dand, Nick / Mucha, Sören / Tsoi, Lam C / Mahil, Satveer K / Stuart, Philip E / Arnold, Andreas / Baurecht, Hansjörg / Burden, A David / Callis Duffin, Kristina / Chandran, Vinod / Curtis, Charles J / Das, Sayantan / Ellinghaus, David / Ellinghaus, Eva / Enerback, Charlotta / Esko, Tõnu / Gladman, Dafna D / Griffiths, Christopher E M / Gudjonsson, Johann E / Hoffman, Per / Homuth, Georg / Hüffmeier, Ulrike / Krueger, Gerald G / Laudes, Matthias / Lee, Sang Hyuck / Lieb, Wolfgang / Lim, Henry W / Löhr, Sabine / Mrowietz, Ulrich / Müller-Nurayid, Martina / Nöthen, Markus / Peters, Annette / Rahman, Proton / Reis, André / Reynolds, Nick J / Rodriguez, Elke / Schmidt, Carsten O / Spain, Sarah L / Strauch, Konstantin / Tejasvi, Trilokraj / Voorhees, John J / Warren, Richard B / Weichenthal, Michael / Weidinger, Stephan / Zawistowski, Matthew / Nair, Rajan P / Capon, Francesca / Smith, Catherine H / Trembath, Richard C / Abecasis, Goncalo R / Elder, James T / Franke, Andre / Simpson, Michael A / Barker, Jonathan N. ·Division of Genetics and Molecular Medicine, Faculty of Life Sciences & Medicine, King's College London, London, UK. · Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany. · Department of Dermatology. · Department of Computational Medicine & Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA. · Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA. · St John's Institute of Dermatology, Faculty of Life Sciences & Medicine, King's College London, London, UK. · Clinic and Polyclinic of Dermatology, University Medicine Greifswald, Greifswald, Germany. · Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. · Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK. · Department of Dermatology, University of Utah, Salt Lake City, UT, USA. · Department of Medicine. · Department of Laboratory Medicine and Pathobiology. · Institute of Medical Science, University of Toronto, Toronto, ON, Canada. · Krembil Research Institute, University Health Network, Toronto, ON, Canada. · NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK. · Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. · Division of Cell Biology and Dermatology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. · Estonian Biobank, Estonian Genome Center, University of Tartu, Tartu, Estonia. · Dermatology Centre, Salford Royal Hospital, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK. · Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland. · Institute of Human Genetics, University of Bonn, Bonn, Germany. · Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany. · Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. · I. Department of Medicine. · Institute of Epidemiology and Biobank PopGen, Christian-Albrechts-University of Kiel, Kiel, Germany. · Department of Dermatology, Henry Ford Hospital, Detroit, MI, USA. · Institute of Genetic Epidemiology, Helmholtz Zentrum Munich, Neuherberg, Germany. · Memorial University of Newfoundland, St. John's, NL, Canada. · Dermatological Sciences, Institute of Cellular Medicine, Newcastle University Medical School, Newcastle upon Tyne, UK. · Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. · Institute for Community Medicine, Study of Health in Pomerania/KEF, University Medicine Greifswald, Greifswald, Germany. · Dermatology Centre, Salford Road NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK. · Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany. · Ann Arbor Veterans Hospital, Ann Arbor, MI, USA. ·Hum Mol Genet · Pubmed #28973304.

ABSTRACT: Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 × 10-8, OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency < 0.01) via gene-wide aggregation testing (IFIH1: pburden = 2.53 × 10-7, OR = 0.707; TYK2: pburden = 6.17 × 10-4, OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.

4 Article The serine protease inhibitor of Kazal-type 7 (SPINK7) is expressed in human skin. 2017

Weber, Clemens / Fischer, Jan / Redelfs, Lisa / Rademacher, Franziska / Harder, Jürgen / Weidinger, Stephan / Wu, Zhihong / Meyer-Hoffert, Ulf. ·Department of Dermatology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Schittenhelmstr. 7, 24105, Kiel, Germany. · Institute of Biochemistry and Cell Biology, Zhejiang University of Science and Technology, Hangzhou, 310023, China. · Department of Dermatology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Schittenhelmstr. 7, 24105, Kiel, Germany. umeyerhoffert@dermatology.uni-kiel.de. ·Arch Dermatol Res · Pubmed #28852849.

ABSTRACT: Proteases and their inhibitors play an important role in epidermal homeostasis. Their imbalance contributes to severe skin diseases. SPINK7 is a member of the SPINK protease inhibitor family and has been described so far as a cancer-related gene in the esophagus. Herein, we describe for the first time its expression in healthy human skin. Moreover, SPINK7 is up-regulated in inflammatory skin diseases like psoriasis and eczema as demonstrated by immunohistochemistry, though real-time PCR analyses revealed no significant up-regulation. In cultured keratinocytes, SPINK7 mRNA expression was up-regulated by IL-17A together with IFNγ. Our observation points to a role of SPINK7 in skin homeostasis and its involvement in inflammatory skin diseases.

5 Article miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis. 2017

Hermann, Helen / Runnel, Toomas / Aab, Alar / Baurecht, Hansjörg / Rodriguez, Elke / Magilnick, Nathaniel / Urgard, Egon / Šahmatova, Liisi / Prans, Ele / Maslovskaja, Julia / Abram, Kristi / Karelson, Maire / Kaldvee, Bret / Reemann, Paula / Haljasorg, Uku / Rückert, Beate / Wawrzyniak, Paulina / Weichenthal, Michael / Mrowietz, Ulrich / Franke, Andre / Gieger, Christian / Barker, Jonathan / Trembath, Richard / Tsoi, Lam C / Elder, James T / Tkaczyk, Eric R / Kisand, Kai / Peterson, Pärt / Kingo, Külli / Boldin, Mark / Weidinger, Stephan / Akdis, Cezmi A / Rebane, Ana. ·Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia. · Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia; Institute of Molecular and Cellular Biology, University of Tartu, Tartu, Estonia. · Department of Dermatology, University Hospital Schleswig-Holstein, Christian-Albrechts-University of Kiel, Kiel, Germany. · Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope National Medical Center, Duarte, California, USA. · Department of Dermatology and Venereology, University of Tartu, Tartu, Estonia; Dermatology Clinic, Tartu University Hospital, Tartu, Estonia. · Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia; Department of Dermatology and Venereology, University of Tartu, Tartu, Estonia. · Dermatology Clinic, Tartu University Hospital, Tartu, Estonia. · Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland. · Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany. · Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Division of Genetics and Molecular Medicine, King's College London, London, UK; St John's Institute of Dermatology, King's College London, London, UK. · Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA; Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan, USA. · Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA. · Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia. Electronic address: ana.rebane@ut.ee. ·J Invest Dermatol · Pubmed #28595995.

ABSTRACT: miR-146a inhibits inflammatory responses in human keratinocytes and in different mouse models of skin inflammation. Little is known about the role of miR-146b in the skin. In this study, we confirmed the increased expression of miR-146a and miR-146b (miR-146a/b) in the lesional skin of patients with psoriasis. The expression of miR-146a was approximately twofold higher than that of miR-146b in healthy human skin, and it was more strongly induced by stimulation of proinflammatory cytokines in keratinocytes and fibroblasts. miR-146a/b target genes regulating inflammatory responses or proliferation were altered in the skin of patients with psoriasis, among which FERMT1 was verified as a direct target of miR-146a. In silico analysis of genome-wide data from >4,000 psoriasis cases and >8,000 controls confirmed a moderate association between psoriasis and genetic variants in the miR-146a encoding gene. Transfection of miR-146a/b suppressed and inhibition enhanced keratinocyte proliferation and the expression of psoriasis-related target genes. Enhanced expression of miR-146a/b-influenced genes was detected in cultured keratinocytes from miR-146a

6 Article Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants. 2017

Tsoi, Lam C / Stuart, Philip E / Tian, Chao / Gudjonsson, Johann E / Das, Sayantan / Zawistowski, Matthew / Ellinghaus, Eva / Barker, Jonathan N / Chandran, Vinod / Dand, Nick / Duffin, Kristina Callis / Enerbäck, Charlotta / Esko, Tõnu / Franke, Andre / Gladman, Dafna D / Hoffmann, Per / Kingo, Külli / Kõks, Sulev / Krueger, Gerald G / Lim, Henry W / Metspalu, Andres / Mrowietz, Ulrich / Mucha, Sören / Rahman, Proton / Reis, Andre / Tejasvi, Trilokraj / Trembath, Richard / Voorhees, John J / Weidinger, Stephan / Weichenthal, Michael / Wen, Xiaoquan / Eriksson, Nicholas / Kang, Hyun M / Hinds, David A / Nair, Rajan P / Abecasis, Gonçalo R / Elder, James T. ·Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. · Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA. · Department of Computational Medicine &Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. · 23andMe, Inc., Mountain View, California 94041, USA. · Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel 24105, Germany. · St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, UK. · Department of Medicine, Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada M5S 1A8. · Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Research Institute, University of Toronto, Toronto, Ontario, Canada M5T 2S8. · Department of Dermatology, University of Utah, Salt Lake City, Utah 84132, USA. · Department of Dermatology, Linköping University, Linköping SE-581 83, Sweden. · Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. · Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. · Institute of Human Genetics, University of Bonn, Bonn 53127, Germany. · Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel 4031, Switzerland. · Dermatology Clinic, Tartu University Hospital, Department of Dermatology and Venereology, University of Tartu, Tartu 50417, Estonia. · Department of Pathophysiology, Centre of Translational Medicine and Centre for Translational Genomics, University of Tartu, Tartu 50411, Estonia. · Department of Reproductive Biology, Estonian University of Life Sciences, Tartu 51006, Estonia. · Department of Dermatology, Henry Ford Hospital, Detroit, Michigan 48202, USA. · Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel 24105, Germany. · Memorial University, St. John's, Newfoundland, Newfoundland and Labrador, Canada A1B 3X9. · Institute of Human Genetics, FAU Erlangen-Nürnberg, Erlangen 91054, Germany. · Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan 48105, USA. · Department of Medical and Molecular Genetics, King's College London, London WC2R 2LS, UK. ·Nat Commun · Pubmed #28537254.

ABSTRACT: Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFκB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8

7 Article A novel molecular disease classifier for psoriasis and eczema. 2016

Garzorz-Stark, Natalie / Krause, Linda / Lauffer, Felix / Atenhan, Anne / Thomas, Jenny / Stark, Sebastian P / Franz, Regina / Weidinger, Stephan / Balato, Anna / Mueller, Nikola S / Theis, Fabian J / Ring, Johannes / Schmidt-Weber, Carsten B / Biedermann, Tilo / Eyerich, Stefanie / Eyerich, Kilian. ·Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany. natalie.garzorz@tum.de. · Institute of Computational Biology, Helmholtz Center Munich, Neuherberg, Germany. · Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany. · ZAUM - Center of Allergy and Environment, Technical University of Munich and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany. · Department of Dermatology, Allergology, and Venereology, University Hospital Schleswig-Holstein, Kiel, Germany. · Dipartimento di Scienze biomediche avanzate, Università degli Studi di Napoli Federico II, Naples, Italy. · Department of Mathematics, Technical University of Munich, Garching, Germany. ·Exp Dermatol · Pubmed #27193975.

ABSTRACT: Novel specific therapies for psoriasis and eczema have been developed, and they mark a new era in the treatment of these complex inflammatory skin diseases. However, within their broad clinical spectrum, psoriasis and eczema phenotypes overlap making an accurate diagnosis impossible in special cases, not to speak about predicting the clinical outcome of an individual patient. Here, we present a novel robust molecular classifier (MC) consisting of NOS2 and CCL27 gene that diagnosed psoriasis and eczema with a sensitivity and specificity of >95% in a cohort of 129 patients suffering from (i) classical forms; (ii) subtypes; and (iii) clinically and histologically indistinct variants of psoriasis and eczema. NOS2 and CCL27 correlated with clinical and histological hallmarks of psoriasis and eczema in a mutually antagonistic way, thus highlighting their biological relevance. In line with this, the MC could be transferred to the level of immunofluorescence stainings for iNOS and CCL27 protein on paraffin-embedded sections, where patients were diagnosed with sensitivity and specificity >88%. Our MC proved superiority over current gold standard methods to distinguish psoriasis and eczema and may therefore build the basis for molecular diagnosis of chronic inflammatory skin diseases required to establish personalized medicine in the field.

8 Article Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. 2016

Ellinghaus, David / Jostins, Luke / Spain, Sarah L / Cortes, Adrian / Bethune, Jörn / Han, Buhm / Park, Yu Rang / Raychaudhuri, Soumya / Pouget, Jennie G / Hübenthal, Matthias / Folseraas, Trine / Wang, Yunpeng / Esko, Tonu / Metspalu, Andres / Westra, Harm-Jan / Franke, Lude / Pers, Tune H / Weersma, Rinse K / Collij, Valerie / D'Amato, Mauro / Halfvarson, Jonas / Jensen, Anders Boeck / Lieb, Wolfgang / Degenhardt, Franziska / Forstner, Andreas J / Hofmann, Andrea / Anonymous3230861 / Anonymous3240861 / Anonymous3250861 / Anonymous3260861 / Anonymous3270861 / Schreiber, Stefan / Mrowietz, Ulrich / Juran, Brian D / Lazaridis, Konstantinos N / Brunak, Søren / Dale, Anders M / Trembath, Richard C / Weidinger, Stephan / Weichenthal, Michael / Ellinghaus, Eva / Elder, James T / Barker, Jonathan N W N / Andreassen, Ole A / McGovern, Dermot P / Karlsen, Tom H / Barrett, Jeffrey C / Parkes, Miles / Brown, Matthew A / Franke, Andre. ·Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany. · Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK. · Nuffield Department of Clinical Neurosciences, Division of Clinical Neurology, John Radcliffe Hospital, University of Oxford, Oxford, UK. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. · Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea. · Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea. · Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. · Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Division of Rheumatology, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA. · Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. · Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. · Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway. · K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway. · Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway. · Department of Neurosciences, University of California, San Diego, La Jolla, California, USA. · Estonian Genome Center, University of Tartu, Tartu, Estonia. · Division of Endocrinology, Boston Children's Hospital, Cambridge, Massachusetts, USA. · Center for Basic and Translational Obesity Research, Boston Children's Hospital, Cambridge, Massachusetts, USA. · University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands. · Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. · Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. · Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands. · Department of Bioscience and Nutrition, Karolinska Institutet, Stockholm, Sweden. · BioCruces Health Research Institute and Ikerbasque, Basque Foundation for Science, Bilbao, Spain. · Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden. · Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Institute of Epidemiology, University Hospital Schleswig-Holstein, Kiel, Germany. · PopGen Biobank, University Hospital Schleswig-Holstein, Kiel, Germany. · Institute of Human Genetics, University of Bonn, Bonn, Germany. · Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. · Department of General Internal Medicine, Universitätsklinikum Schleswig-Holstein Campus Kiel, Kiel, Germany. · Department of Dermatology, University Hospital, Schleswig-Holstein, Christian Albrechts University of Kiel, Kiel, Germany. · Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Hepatology, Mayo Clinic, College of Medicine, Rochester, Minnesota, USA. · Department of Radiology, University of California, San Diego, La Jolla, California, USA. · Division of Genetics and Molecular Medicine, King's College London, London, UK. · Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA. · Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan, USA. · St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London, London, UK. · NORMENT, K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Oslo, Norway. · F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Los Angeles, California, USA. · Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. · Inflammatory Bowel Disease Research Group, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK. · University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia. · Institute of Health and Biomedical Innovation (IHBI), Faculty of Health, Queensland University of Technology (QUT), Translational Research Institute, Brisbane, Queensland, Australia. ·Nat Genet · Pubmed #26974007.

ABSTRACT: We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European ancestry, we identified 244 independent multidisease signals, including 27 new genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multidisease signals with expression data sets from human, rat and mouse together with epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases genetically identical to those with another disease, possibly owing to diagnostic misclassification, molecular subtypes or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes.

9 Article Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture. 2015

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. ·Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. · 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 48109, USA. · Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Ann Arbor Veterans Affairs Hospital, Ann Arbor, MI 48105, USA. · Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA. · Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany. · 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. · Department of Dermatology, University of Utah, Salt Lake City, UT 84132, USA. · Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA. · Department of Clinical and Experimental Medicine, Division of Cell Biology and Dermatology, Linköping University, 581 83 Linköping, Sweden. · 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. · Dermatology Clinic, Tartu University Hospital, Department of Dermatology and Venereology, University of Tartu, 50417 Tartu, Estonia. · Estonian Genome Center, University of Tartu, 51010 Tartu, Estonia. · Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany. · Institute of Human Genetics, University of Erlangen-Nuremberg, 91054 Erlangen, Germany. · 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, Technical University Munich, 80333 Munich, Germany. · 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. · Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, 53127 Bonn, Germany. · 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. · Department of Dermatology, Venereology and Allergology, University of Leipzig, 04103 Leipzig, Germany. · Saint Paul Rheumatology, Eagan, MN 55121, USA. · Seattle Rheumatology Associates, 601 Broadway, Suite 600, Seattle, WA 98122, USA. · Allergy, Immunology, and Rheumatology Division, University of Rochester Medical Center, Rochester, NY 14623, USA. · National Heart and Lung Institute, Imperial College, London SW7 2AZ, UK. · Department of Dermatology, Henry Ford Hospital, Detroit, MI 48202, USA. · Memorial University, St. John's, NL A1C 5B8, Canada. · The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY 11030, USA. · 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 · Pubmed #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.

10 Article Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci. 2015

Tsoi, Lam C / Spain, Sarah L / Ellinghaus, Eva / Stuart, Philip E / Capon, Francesca / Knight, Jo / Tejasvi, Trilokraj / Kang, Hyun M / Allen, Michael H / Lambert, Sylviane / Stoll, Stefan W / Weidinger, Stephan / Gudjonsson, Johann E / Koks, Sulev / Kingo, Külli / Esko, Tonu / Das, Sayantan / Metspalu, Andres / Weichenthal, Michael / Enerback, Charlotta / Krueger, Gerald G / Voorhees, John J / Chandran, Vinod / Rosen, Cheryl F / Rahman, Proton / Gladman, Dafna D / Reis, Andre / Nair, Rajan P / Franke, Andre / Barker, Jonathan N W N / Abecasis, Goncalo R / Trembath, Richard C / Elder, James T. ·Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA. · Division of Genetics and Molecular Medicine, King's College London, London WC2R 2LS, UK. · Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. · Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany. · Department of Dermatology, University of Michigan, Ann Arbor, Michigan 48109, USA. · Neuroscience Research, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8. · National Institute for Health Research (NIHR), Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust, London SE1 9RT, UK. · Department of Dermatology, University Hospital, Schleswig-Holstein, Christian-Albrechts-University, 24105 Kiel, Germany. · Department of Pathophysiology, Centre of Translational Medicine and Centre for Translational Genomics, University of Tartu, 50409 Tartu, Estonia. · Department of Dermatology and Venereology, University of Tartu, 50409 Tartu, Estonia. · Estonian Genome Center, University of Tartu, 51010 Tartu, Estonia. · Department of Dermatology, Linköping University, SE-581 83 Linköping, Sweden. · Department of Dermatology, University of Utah, Salt Lake City, Utah 84132, USA. · Department of Medicine, Division of Rheumatology, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada M5T 2S8. · Department of Medicine, Division of Dermatology, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada M5T 2S8. · Department of Medicine, Memorial University, St John's, Newfoundland, Canada A1C 5B8. · Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen 91054, Germany. · Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AD, UK. · Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan 48105, USA. ·Nat Commun · Pubmed #25939698.

ABSTRACT: Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genome-wide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susceptibility loci. Here, we extend our previous meta-analysis of European ancestry by refined genotype calling and imputation and by the addition of 5,033 cases and 5,707 controls. The combined analysis, consisting of over 15,000 cases and 27,000 controls, identifies five new psoriasis susceptibility loci at genome-wide significance (P<5 × 10(-8)). The newly identified signals include two that reside in intergenic regions (1q31.1 and 5p13.1) and three residing near PLCL2 (3p24.3), NFKBIZ (3q12.3) and CAMK2G (10q22.2). We further demonstrate that NFKBIZ is a TRAF3IP2-dependent target of IL-17 signalling in human skin keratinocytes, thereby functionally linking two strong candidate genes. These results further integrate the genetics and immunology of psoriasis, suggesting new avenues for functional analysis and improved therapies.

11 Article Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility. 2015

Yin, Xianyong / Low, Hui Qi / Wang, Ling / Li, Yonghong / Ellinghaus, Eva / Han, Jiali / Estivill, Xavier / Sun, Liangdan / Zuo, Xianbo / Shen, Changbing / Zhu, Caihong / Zhang, Anping / Sanchez, Fabio / Padyukov, Leonid / Catanese, Joseph J / Krueger, Gerald G / Duffin, Kristina Callis / Mucha, Sören / Weichenthal, Michael / Weidinger, Stephan / Lieb, Wolfgang / Foo, Jia Nee / Li, Yi / Sim, Karseng / Liany, Herty / Irwan, Ishak / Teo, Yikying / Theng, Colin T S / Gupta, Rashmi / Bowcock, Anne / De Jager, Philip L / Qureshi, Abrar A / de Bakker, Paul I W / Seielstad, Mark / Liao, Wilson / Ståhle, Mona / Franke, Andre / Zhang, Xuejun / Liu, Jianjun. ·1] Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui 230032, China [2] State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, Anhui 230032, China [3] Key Lab of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui 230032, China [4] Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui 230032, China. · Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore. · Celera, Alameda, California 94502, USA. · Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelm Street 12, Kiel 24105, Germany. · 1] Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana 46202, USA [2] Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana 46202, USA [3] Department of Dermatology, School of Medicine, Indiana University, Indianapolis, Indiana 46202, USA. · 1] Genetic Causes of Disease Group, Centre for Genomic Regulation (CRG), Barcelona, Catalonia, E-08003, Spain [2] Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Catalonia, E-08003, Spain [3] Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, E-08003, Spain [4] CIBER in Epidemiology and Public Health (CIBERESP), Barcelona, Catalonia, E-08003, Spain. · Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm 17176, Sweden. · Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm 17177, Sweden. · Department of Dermatology, University of Utah, Salt Lake, Utah 84132, USA. · Department of Dermatology, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany. · Institute of Epidemiology and Biobank PopGen, Christian Albrechts University, Kiel, Germany. · 1] Departments of Statistics and Applied Probability, National University of Singapore, Singapore 138672, Singapore [2] Department of Epidemiology and Public Health, National University of Singapore, Singapore 138672, Singapore. · National Skin Centre, Singapore 308205, Singapore. · Department of Dermatology, University of California San Francisco, San Francisco, California 94115, USA. · National Heart and Lung Institute, Imperial College, London SW3 6LY, UK. · 1] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02138, USA [2] Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham &Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. · 1] Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana 46202, USA [2] Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana 46202, USA [3] Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham &Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. · 1] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands [2] Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands. · 1] Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore [2] Institute for Human Genetics, University of California San Francisco, San Francisco, California 94143, USA. · 1] State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, Anhui 230032, China [2] Key Lab of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui 230032, China [3] Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui 230032, China [4] Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore [5] Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore, 138672, Singapore [6] School of Life Sciences, Anhui Medical University, Hefei, Anhui 230032, China. ·Nat Commun · Pubmed #25903422.

ABSTRACT: Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.

12 Article Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures. 2015

Koch, Manja / Baurecht, Hansjörg / Ried, Janina S / Rodriguez, Elke / Schlesinger, Sabrina / Volks, Natalie / Gieger, Christian / Rückert, Ina-Maria / Heinrich, Luise / Willenborg, Christina / Smith, Catherine / Peters, Annette / Thorand, Barbara / Koenig, Wolfgang / Lamina, Claudia / Jansen, Henning / Kronenberg, Florian / Seissler, Jochen / Thiery, Joachim / Rathmann, Wolfgang / Schunkert, Heribert / Erdmann, Jeanette / Barker, Jonathan / Nair, Rajan P / Tsoi, Lam C / Elder, James T / Mrowietz, Ulrich / Weichenthal, Michael / Mucha, Sören / Schreiber, Stefan / Franke, Andre / Schmitt, Jochen / Lieb, Wolfgang / Weidinger, Stephan. ·Institute of Epidemiology, Christian-Albrechts University Kiel, Kiel, Germany. · Department of Dermatology, Allergology, and Venerology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. · Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Center for Evidence-Based Healthcare, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. · Institute for Integrative und Experimental Genomics and DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany. · St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, Kings College London, London, UK. · Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany. · Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria. · Deutsches Herzzentrum Munich, Technische Universität Munich, Munich, Germany. · Medizinische Klinik und Poliklinik IV, Diabetes Zentrum, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany. · Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany. · German Diabetes Center, Leibniz Institute at Heinrich Heine University Düsseldorf, Institute of Biometrics and Epidemiology, Düsseldorf, Germany. · Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA. · Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA. · Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA; Ann-Arbor Veteran Affairs Hospital, Ann Arbor, Michigan, USA. · Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany. · Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany. · Center for Evidence-Based Healthcare, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany; These authors contributed equally to this work. · Institute of Epidemiology, Christian-Albrechts University Kiel, Kiel, Germany; These authors contributed equally to this work. · Department of Dermatology, Allergology, and Venerology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; These authors contributed equally to this work.. Electronic address: sweidinger@dermatology.uni-kiel.de. ·J Invest Dermatol · Pubmed #25599394.

ABSTRACT: Psoriasis has been linked to cardiometabolic diseases, but epidemiological findings are inconsistent. We investigated the association between psoriasis and cardiometabolic outcomes in a German cross-sectional study (n=4,185) and a prospective cohort of German Health Insurance beneficiaries (n=1,811,098). A potential genetic overlap was explored using genome-wide data from >22,000 coronary artery disease and >4,000 psoriasis cases, and with a dense genotyping study of cardiometabolic risk loci on 927 psoriasis cases and 3,717 controls. After controlling for major confounders, in the cross-sectional analysis psoriasis was significantly associated with type 2 diabetes (T2D, adjusted odds ratio (OR)=2.36; 95% confidence interval CI=1.26-4.41) and myocardial infarction (MI, OR=2.26; 95% CI=1.03-4.96). In the longitudinal study, psoriasis slightly increased the risk for incident T2D (adjusted relative risk (RR)=1.11; 95% CI=1.08-1.14) and MI (RR=1.14; 95% CI=1.06-1.22), with highest risk increments in systemically treated psoriasis, which accounted for 11 and 17 excess cases of T2D and MI per 10,000 person-years. Except for weak signals from within the major histocompatibility complex, there was no evidence of genetic risk loci shared between psoriasis and cardiometabolic traits. Our findings suggest that psoriasis, in particular severe psoriasis, increases the risk for T2D and MI, and that the genetic architecture of psoriasis and cardiometabolic traits is largely distinct.

13 Article Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms. 2015

Baurecht, Hansjörg / Hotze, Melanie / Brand, Stephan / Büning, Carsten / Cormican, Paul / Corvin, Aiden / Ellinghaus, David / Ellinghaus, Eva / Esparza-Gordillo, Jorge / Fölster-Holst, Regina / Franke, Andre / Gieger, Christian / Hubner, Norbert / Illig, Thomas / Irvine, Alan D / Kabesch, Michael / Lee, Young A E / Lieb, Wolfgang / Marenholz, Ingo / McLean, W H Irwin / Morris, Derek W / Mrowietz, Ulrich / Nair, Rajan / Nöthen, Markus M / Novak, Natalija / O'Regan, Grainne M / Anonymous2730817 / Schreiber, Stefan / Smith, Catherine / Strauch, Konstantin / Stuart, Philip E / Trembath, Richard / Tsoi, Lam C / Weichenthal, Michael / Barker, Jonathan / Elder, James T / Weidinger, Stephan / Cordell, Heather J / Brown, Sara J. ·Department of Dermatology, Allergology, and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany. · Department of Medicine II - Grosshadern, Ludwig-Maximilians-University (LMU), 81377 Munich, Germany. · Department of Gastroenterology, Hepatology and Endocrinology, Charité, Campus Mitte, 10117 Berlin, Germany. · Neuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland. · Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany. · Max-Delbrück-Centrum (MDC) for Molecular Medicine, Berlin-Buch, 13092 Berlin, Germany; Pediatric Allergy, Experimental and Clinical Research Center, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany. · Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany; Research Unit of Molecular Epidemiology, 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. · Max-Delbrück-Centrum (MDC) for Molecular Medicine, Berlin-Buch, 13092 Berlin, Germany. · Research Unit of Molecular Epidemiology, German Research Center for Environmental Health, 85764 Neuherberg, Germany; Hannover Unified Biobank, Hannover Medical School, 30625 Hannover, Germany. · Department of Paediatric Dermatology, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland; National Children's Research Centre, Dublin 12, Ireland; Department of Clinical Medicine, Trinity College Dublin, Dublin 2, Ireland. · Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), 93042 Regensburg, Germany. · Institute of Epidemiology and PopGen Biobank, University Hospital Schleswig-Holstein, 24105 Kiel, Germany. · Dermatology and Genetic Medicine, College of Life Sciences and College of Medicine, Dentistry & Nursing, University of Dundee, Dundee DD1 5EH, UK. · Neuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland; Cognitive Genetics and Therapy Group, School of Psychology and Discipline of Biochemistry, National University of Ireland, Galway, Ireland. · Department of Dermatology, University of Michigan, Ann Arbor, MI 48109-5675, USA. · Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, 53127 Bonn, Germany. · Department of Dermatology and Allergy, University of Bonn Medical Center, 53105 Bonn, Germany. · Department of Paediatric Dermatology, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland. · Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany; Department of Internal Medicine, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany. · Division of Genetics and Molecular Medicine, St John's Institute of Dermatology, Kings College London, London SE1 9RT, UK. · Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, 80539 Munich, Germany. · Queen Mary University of London, Barts and the London School of Medicine and Dentistry, London E1 4NS, UK. · Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109-5314, USA. · Department of Dermatology, University of Michigan, Ann Arbor, MI 48109-5675, USA; Ann Arbor Veterans Affairs Hospital, Ann Arbor, MI 48105, USA. · Department of Dermatology, Allergology, and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany. Electronic address: sweidinger@dermatology.uni-kiel.de. · Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK. · Dermatology and Genetic Medicine, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK. Electronic address: s.j.brown@dundee.ac.uk. ·Am J Hum Genet · Pubmed #25574825.

ABSTRACT: Atopic dermatitis and psoriasis are the two most common immune-mediated inflammatory disorders affecting the skin. Genome-wide studies demonstrate a high degree of genetic overlap, but these diseases have mutually exclusive clinical phenotypes and opposing immune mechanisms. Despite their prevalence, atopic dermatitis and psoriasis very rarely co-occur within one individual. By utilizing genome-wide association study and ImmunoChip data from >19,000 individuals and methodologies developed from meta-analysis, we have identified opposing risk alleles at shared loci as well as independent disease-specific loci within the epidermal differentiation complex (chromosome 1q21.3), the Th2 locus control region (chromosome 5q31.1), and the major histocompatibility complex (chromosome 6p21-22). We further identified previously unreported pleiotropic alleles with opposing effects on atopic dermatitis and psoriasis risk in PRKRA and ANXA6/TNIP1. In contrast, there was no evidence for shared loci with effects operating in the same direction on both diseases. Our results show that atopic dermatitis and psoriasis have distinct genetic mechanisms with opposing effects in shared pathways influencing epidermal differentiation and immune response. The statistical analysis methods developed in the conduct of this study have produced additional insight from previously published data sets. The approach is likely to be applicable to the investigation of the genetic basis of other complex traits with overlapping and distinct clinical features.

14 Article A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis. 2013

Weidinger, Stephan / Willis-Owen, Saffron A G / Kamatani, Yoichiro / Baurecht, Hansjörg / Morar, Nilesh / Liang, Liming / Edser, Pauline / Street, Teresa / Rodriguez, Elke / O'Regan, Grainne M / Beattie, Paula / Fölster-Holst, Regina / Franke, Andre / Novak, Natalija / Fahy, Caoimhe M / Winge, Mårten C G / Kabesch, Michael / Illig, Thomas / Heath, Simon / Söderhäll, Cilla / Melén, Erik / Pershagen, Göran / Kere, Juha / Bradley, Maria / Lieden, Agne / Nordenskjold, Magnus / Harper, John I / McLean, W H Irwin / Brown, Sara J / Cookson, William O C / Lathrop, G Mark / Irvine, Alan D / Moffatt, Miriam F. ·Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein and. ·Hum Mol Genet · Pubmed #23886662.

ABSTRACT: Atopic dermatitis (AD) is the most common dermatological disease of childhood. Many children with AD have asthma and AD shares regions of genetic linkage with psoriasis, another chronic inflammatory skin disease. We present here a genome-wide association study (GWAS) of childhood-onset AD in 1563 European cases with known asthma status and 4054 European controls. Using Illumina genotyping followed by imputation, we generated 268 034 consensus genotypes and in excess of 2 million single nucleotide polymorphisms (SNPs) for analysis. Association signals were assessed for replication in a second panel of 2286 European cases and 3160 European controls. Four loci achieved genome-wide significance for AD and replicated consistently across all cohorts. These included the epidermal differentiation complex (EDC) on chromosome 1, the genomic region proximal to LRRC32 on chromosome 11, the RAD50/IL13 locus on chromosome 5 and the major histocompatibility complex (MHC) on chromosome 6; reflecting action of classical HLA alleles. We observed variation in the contribution towards co-morbid asthma for these regions of association. We further explored the genetic relationship between AD, asthma and psoriasis by examining previously identified susceptibility SNPs for these diseases. We found considerable overlap between AD and psoriasis together with variable coincidence between allergic rhinitis (AR) and asthma. Our results indicate that the pathogenesis of AD incorporates immune and epidermal barrier defects with combinations of specific and overlapping effects at individual loci.

15 Article Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. 2012

Tsoi, Lam C / Spain, Sarah L / Knight, Jo / Ellinghaus, Eva / Stuart, Philip E / Capon, Francesca / Ding, Jun / Li, Yanming / Tejasvi, Trilokraj / Gudjonsson, Johann E / Kang, Hyun M / Allen, Michael H / McManus, Ross / Novelli, Giuseppe / Samuelsson, Lena / Schalkwijk, Joost / Ståhle, Mona / Burden, A David / Smith, Catherine H / Cork, Michael J / Estivill, Xavier / Bowcock, Anne M / Krueger, Gerald G / Weger, Wolfgang / Worthington, Jane / Tazi-Ahnini, Rachid / Nestle, Frank O / Hayday, Adrian / Hoffmann, Per / Winkelmann, Juliane / Wijmenga, Cisca / Langford, Cordelia / Edkins, Sarah / Andrews, Robert / Blackburn, Hannah / Strange, Amy / Band, Gavin / Pearson, Richard D / Vukcevic, Damjan / Spencer, Chris C A / Deloukas, Panos / Mrowietz, Ulrich / Schreiber, Stefan / Weidinger, Stephan / Koks, Sulev / Kingo, Külli / Esko, Tonu / Metspalu, Andres / Lim, Henry W / Voorhees, John J / Weichenthal, Michael / Wichmann, H Erich / Chandran, Vinod / Rosen, Cheryl F / Rahman, Proton / Gladman, Dafna D / Griffiths, Christopher E M / Reis, Andre / Kere, Juha / Anonymous6390741 / Anonymous6400741 / Anonymous6410741 / Anonymous6420741 / Nair, Rajan P / Franke, Andre / Barker, Jonathan N W N / Abecasis, Goncalo R / Elder, James T / Trembath, Richard C. ·Department of Biostatistics, Center for Statistical Genetics, University of Michigan Ann Arbor, MI, USA. ·Nat Genet · Pubmed #23143594.

ABSTRACT: To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.

16 Article Combined analysis of genome-wide association studies for Crohn disease and psoriasis identifies seven shared susceptibility loci. 2012

Ellinghaus, David / Ellinghaus, Eva / Nair, Rajan P / Stuart, Philip E / Esko, Tõnu / Metspalu, Andres / Debrus, Sophie / Raelson, John V / Tejasvi, Trilokraj / Belouchi, Majid / West, Sarah L / Barker, Jonathan N / Kõks, Sulev / Kingo, Külli / Balschun, Tobias / Palmieri, Orazio / Annese, Vito / Gieger, Christian / Wichmann, H Erich / Kabesch, Michael / Trembath, Richard C / Mathew, Christopher G / Abecasis, Gonçalo R / Weidinger, Stephan / Nikolaus, Susanna / Schreiber, Stefan / Elder, James T / Weichenthal, Michael / Nothnagel, Michael / Franke, Andre. ·Institute of Clinical Molecular Biology, Christian-Albrechts-University, 24105 Kiel, Germany. ·Am J Hum Genet · Pubmed #22482804.

ABSTRACT: Psoriasis (PS) and Crohn disease (CD) have been shown to be epidemiologically, pathologically, and therapeutically connected, but little is known about their shared genetic causes. We performed meta-analyses of five published genome-wide association studies on PS (2,529 cases and 4,955 controls) and CD (2,142 cases and 5,505 controls), followed up 20 loci that showed strongest evidence for shared disease association and, furthermore, tested cross-disease associations for previously reported PS and CD risk alleles in additional 6,115 PS cases, 4,073 CD cases, and 10,100 controls. We identified seven susceptibility loci outside the human leukocyte antigen region (9p24 near JAK2, 10q22 at ZMIZ1, 11q13 near PRDX5, 16p13 near SOCS1, 17q21 at STAT3, 19p13 near FUT2, and 22q11 at YDJC) shared between PS and CD with genome-wide significance (p < 5 × 10(-8)) and confirmed four already established PS and CD risk loci (IL23R, IL12B, REL, and TYK2). Three of the shared loci are also genome-wide significantly associated with PS alone (10q22 at ZMIZ1, p(rs1250544) = 3.53 × 10(-8), 11q13 near PRDX5, p(rs694739) = 3.71 × 10(-09), 22q11 at YDJC, p(rs181359) = 8.02 × 10(-10)). In addition, we identified one susceptibility locus for CD (16p13 near SOCS1, p(rs4780355) = 4.99 × 10(-8)). Refinement of association signals identified shared genome-wide significant associations for exonic SNPs at 10q22 (ZMIZ1) and in silico expression quantitative trait locus analyses revealed that the associations at ZMIZ1 and near SOCS1 have a potential functional effect on gene expression. Our results show the usefulness of joint analyses of clinically distinct immune-mediated diseases and enlarge the map of shared genetic risk loci.

17 Article Genome-wide meta-analysis of psoriatic arthritis identifies susceptibility locus at REL. 2012

Ellinghaus, Eva / Stuart, Philip E / Ellinghaus, David / Nair, Rajan P / Debrus, Sophie / Raelson, John V / Belouchi, Majid / Tejasvi, Trilokraj / Li, Yanming / Tsoi, Lam C / Onken, Anna T / Esko, Tonu / Metspalu, Andres / Rahman, Proton / Gladman, Dafna D / Bowcock, Anne M / Helms, Cynthia / Krueger, Gerald G / Koks, Sulev / Kingo, Külli / Gieger, Christian / Wichmann, H Erich / Mrowietz, Ulrich / Weidinger, Stephan / Schreiber, Stefan / Abecasis, Gonçalo R / Elder, James T / Weichenthal, Michael / Franke, Andre. ·Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel, Germany. e.ellinghaus@ikmb.uni-kiel.de ·J Invest Dermatol · Pubmed #22170493.

ABSTRACT: Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease affecting up to 30% of psoriasis vulgaris (PsV) cases and approximately 0.25 to 1% of the general population. To identify common susceptibility loci, we performed a meta-analysis of three imputed genome-wide association studies (GWAS) on psoriasis, stratified for PsA. A total of 1,160,703 single-nucleotide polymorphisms (SNPs) were analyzed in the discovery set consisting of 535 PsA cases and 3,432 controls from Germany, the United States, and Canada. We followed up two SNPs in 1,931 PsA cases and 6,785 controls comprising six independent replication panels from Germany, Estonia, the United States, and Canada. In the combined analysis, a genome-wide significant association was detected at 2p16 near the REL locus encoding c-Rel (rs13017599, P=1.18 × 10(-8), odds ratio (OR)=1.27, 95% confidence interval (CI)=1.18-1.35). The rs13017599 polymorphism is known to associate with rheumatoid arthritis (RA), and another SNP near REL (rs702873) was recently implicated in PsV susceptibility. However, conditional analysis indicated that rs13017599, rather than rs702873, accounts for the PsA association at REL. We hypothesize that c-Rel, as a member of the Rel/NF-κB family, is associated with PsA in the context of disease pathways that involve other identified PsA and PsV susceptibility genes including TNIP1, TNFAIP3, and NFκBIA.

18 Article Mutual antagonism of T cells causing psoriasis and atopic eczema. 2011

Eyerich, Stefanie / Onken, Anna T / Weidinger, Stephan / Franke, Andre / Nasorri, Francesca / Pennino, Davide / Grosber, Martine / Pfab, Florian / Schmidt-Weber, Carsten B / Mempel, Martin / Hein, Ruediger / Ring, Johannes / Cavani, Andrea / Eyerich, Kilian. ·Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Center Munich, Munich, Germany. ·N Engl J Med · Pubmed #21774711.

ABSTRACT: -- No abstract --

19 Article [Genetics of common chronic inflammatory skin diseases : An update on atopic dermatitis and psoriasis]. 2011

Rodríguez, E / Eyerich, K / Weidinger, S. ·Klinik und Poliklinik für Dermatologie und Allergologie, Technische Universität München, Germany. elke.rodriguez@helmholtz-muenchen.de ·Hautarzt · Pubmed #21271233.

ABSTRACT: Atopic dermatitis and psoriasis are two common chronic inflammatory skin diseases. Both are multifactorial disorders caused by an interaction between genetic and environmental factors. Epidemiological studies estimated a high heritability of up to 80% for both diseases, indicating a major role of genetic susceptibility factors in disease development and progression. However, in contrast to monogenic disorders, complex diseases are not caused by single gene mutations, but are the result of a complicated network of numerous susceptibility loci, many of which exert additive or synergistic effects, but have only a small role when considered in isolation. Knowledge on the genetic architecture of atopic dermatitis and psoriasis is still incomplete, but major advances have been made in the past years, in particular through genome-wide association approaches.

20 Article Genome-wide association analysis identifies three psoriasis susceptibility loci. 2010

Stuart, Philip E / Nair, Rajan P / Ellinghaus, Eva / Ding, Jun / Tejasvi, Trilokraj / Gudjonsson, Johann E / Li, Yun / Weidinger, Stephan / Eberlein, Bernadette / Gieger, Christian / Wichmann, H Erich / Kunz, Manfred / Ike, Robert / Krueger, Gerald G / Bowcock, Anne M / Mrowietz, Ulrich / Lim, Henry W / Voorhees, John J / Abecasis, Gonçalo R / Weichenthal, Michael / Franke, Andre / Rahman, Proton / Gladman, Dafna D / Elder, James T. ·Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA. ·Nat Genet · Pubmed #20953189.

ABSTRACT: We carried out a meta-analysis of two recent psoriasis genome-wide association studies with a combined discovery sample of 1,831 affected individuals (cases) and 2,546 controls. One hundred and two loci selected based on P value rankings were followed up in a three-stage replication study including 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland and Germany. In the combined meta-analysis, we identified three new susceptibility loci, including one at NOS2 (rs4795067, combined P = 4 × 10⁻¹¹), one at FBXL19 (rs10782001, combined P = 9 × 10⁻¹⁰) and one near PSMA6-NFKBIA (rs12586317, combined P = 2 × 10⁻⁸). All three loci were also associated with psoriatic arthritis (rs4795067, combined P = 1 × 10⁻⁵; rs10782001, combined P = 4 × 10⁻⁸; and rs12586317, combined P = 6 × 1⁻⁵) and purely cutaneous psoriasis (rs4795067, combined P = 1 × 10⁻⁸; rs10782001, combined P = 2 × 10⁻⁶; and rs12586317, combined P = 1 × 10⁻⁶). We also replicated a recently identified association signal near RNF114 (rs495337, combined P = 2 × 10⁻⁷).

21 Article Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2. 2010

Ellinghaus, Eva / Ellinghaus, David / Stuart, Philip E / Nair, Rajan P / Debrus, Sophie / Raelson, John V / Belouchi, Majid / Fournier, Hélène / Reinhard, Claudia / Ding, Jun / Li, Yun / Tejasvi, Trilokraj / Gudjonsson, Johann / Stoll, Stefan W / Voorhees, John J / Lambert, Sylviane / Weidinger, Stephan / Eberlein, Bernadette / Kunz, Manfred / Rahman, Proton / Gladman, Dafna D / Gieger, Christian / Wichmann, H Erich / Karlsen, Tom H / Mayr, Gabriele / Albrecht, Mario / Kabelitz, Dieter / Mrowietz, Ulrich / Abecasis, Gonçalo R / Elder, James T / Schreiber, Stefan / Weichenthal, Michael / Franke, Andre. ·Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany. ·Nat Genet · Pubmed #20953188.

ABSTRACT: Psoriasis is a multifactorial skin disease characterized by epidermal hyperproliferation and chronic inflammation, the most common form of which is psoriasis vulgaris (PsV). We present a genome-wide association analysis of 2,339,118 SNPs in 472 PsV cases and 1,146 controls from Germany, with follow-up of the 147 most significant SNPs in 2,746 PsV cases and 4,140 controls from three independent replication panels. We identified an association at TRAF3IP2 on 6q21 and genotyped two SNPs at this locus in two additional replication panels (the combined discovery and replication panels consisted of 6,487 cases and 8,037 controls; combined P = 2.36 × 10⁻¹⁰ for rs13210247 and combined P = 1.24 × 10⁻¹⁶ for rs33980500). About 15% of psoriasis cases develop psoriatic arthritis (PsA). A stratified analysis of our datasets including only PsA cases (1,922 cases compared to 8,037 controls, P = 4.57 × 10⁻¹² for rs33980500) suggested that TRAF3IP2 represents a shared susceptibility for PsV and PsA. TRAF3IP2 encodes a protein involved in IL-17 signaling and which interacts with members of the Rel/NF-κB transcription factor family.