GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets

Nick Dand, Philip E. Stuart, John Bowes, David Ellinghaus, Joanne Nititham, Jake R. Saklatvala, Maris Teder-Laving, Laurent F. Thomas, Tanel Traks, Steffen Uebe, Gunter Assmann, David Baudry, Frank Behrens, Allison C. Billi, Matthew A. Brown, Harald Burkhardt, Francesca Capon, Raymond Chung, Charles J. Curtis, Michael Duckworth, Eva Ellinghaus, Oliver FitzGerald, Sascha Gerdes, Christopher E. M. Griffiths, Susanne Gulliver, Philip S. Helliwell, Pauline Ho, Per Hoffmann, Oddgeir L. Holmen, Zhi-ming Huang, Kristian Hveem, Deepak Jadon, Michaela Köhm, Cornelia Kraus, Céline Lamacchia, Sang Hyuck Lee, Feiyang Ma, Satveer K. Mahil, Neil McHugh, Ross McManus, Ellen H. Modalsli, Michael J. Nissen, Markus Nöthen, Vinzenz Oji, Jorge R. Oksenberg, Matthew T. Patrick, Bethany E. Perez White, Andreas Ramming, Jürgen Rech, Cheryl Rosen, Mrinal K. Sarkar, Georg Schett, Börge Schmidt, Trilokraj Tejasvi, Heiko Traupe, John J. Voorhees, Eike Matthias Wacker, Richard B. Warren, Rachael Wasikowski, Stephan Weidinger, Xiaoquan Wen, Zhaolin Zhang, Anne Barton, Vinod Chandran, Tõnu Esko, John Foerster, Andre Franke, Dafna D. Gladman, Johann E. Gudjonsson, Wayne Gulliver, Ulrike Hüffmeier, Külli Kingo, Sulev Kõks, Wilson Liao, Mari Løset, Reedik Mägi, Rajan P. Nair, Proton Rahman, André Reis, Catherine H. Smith, Paola Di Meglio, Jonathan N. Barker, Lam C. Tsoi, Michael A. Simpson () and James T. Elder ()
Additional contact information
Nick Dand: King’s College London
Philip E. Stuart: University of Michigan Medical School
John Bowes: The University of Manchester
David Ellinghaus: Christian-Albrechts-University of Kiel
Joanne Nititham: University of California San Francisco
Jake R. Saklatvala: King’s College London
Maris Teder-Laving: University of Tartu
Laurent F. Thomas: NTNU - Norwegian University of Science and Technology
Tanel Traks: University of Tartu
Steffen Uebe: FAU Erlangen-Nürnberg
Gunter Assmann: Department of Rheumatology
David Baudry: King’s College London
Frank Behrens: Goethe University
Allison C. Billi: University of Michigan Medical School
Matthew A. Brown: King’s College London
Harald Burkhardt: Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
Francesca Capon: King’s College London
Raymond Chung: Camberwell
Charles J. Curtis: Camberwell
Michael Duckworth: King’s College London
Eva Ellinghaus: Christian-Albrechts-University of Kiel
Oliver FitzGerald: University College Dublin
Sascha Gerdes: Campus Kiel
Christopher E. M. Griffiths: King’s College London
Susanne Gulliver: Newlab Clinical Research Inc
Philip S. Helliwell: University of Leeds
Pauline Ho: The University of Manchester
Per Hoffmann: School of Medicine & University Hospital Bonn
Oddgeir L. Holmen: NTNU - Norwegian University of Science and Technology
Zhi-ming Huang: University of California San Francisco
Kristian Hveem: NTNU - Norwegian University of Science and Technology
Deepak Jadon: University of Cambridge
Michaela Köhm: Goethe University
Cornelia Kraus: FAU Erlangen-Nürnberg
Céline Lamacchia: Geneva University Hospital
Sang Hyuck Lee: Camberwell
Feiyang Ma: University of Michigan Medical School
Satveer K. Mahil: King’s College London
Neil McHugh: University of Bath
Ross McManus: Trinity College Dublin
Ellen H. Modalsli: NTNU - Norwegian University of Science and Technology
Michael J. Nissen: Geneva University Hospital
Markus Nöthen: School of Medicine & University Hospital Bonn
Vinzenz Oji: University of Münster
Jorge R. Oksenberg: University of California
Matthew T. Patrick: University of Michigan Medical School
Bethany E. Perez White: Northwestern University
Andreas Ramming: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Jürgen Rech: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Cheryl Rosen: University of Toronto
Mrinal K. Sarkar: University of Michigan Medical School
Georg Schett: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Börge Schmidt: University of Duisburg-Essen
Trilokraj Tejasvi: University of Michigan Medical School
Heiko Traupe: University of Münster
John J. Voorhees: University of Michigan Medical School
Eike Matthias Wacker: Christian-Albrechts-University of Kiel
Richard B. Warren: The University of Manchester
Rachael Wasikowski: University of Michigan Medical School
Stephan Weidinger: Campus Kiel
Xiaoquan Wen: University of Michigan
Zhaolin Zhang: University of Michigan Medical School
Anne Barton: The University of Manchester
Vinod Chandran: University Health Network and University of Toronto
Tõnu Esko: University of Tartu
John Foerster: University of Dundee
Andre Franke: Christian-Albrechts-University of Kiel
Dafna D. Gladman: University Health Network and University of Toronto
Johann E. Gudjonsson: University of Michigan Medical School
Wayne Gulliver: Newlab Clinical Research Inc
Ulrike Hüffmeier: FAU Erlangen-Nürnberg
Külli Kingo: University of Tartu
Sulev Kõks: Perron Institute for Neurological and Translational Science
Wilson Liao: University of California San Francisco
Mari Løset: NTNU - Norwegian University of Science and Technology
Reedik Mägi: University of Tartu
Rajan P. Nair: University of Michigan Medical School
Proton Rahman: Memorial University of Newfoundland
André Reis: FAU Erlangen-Nürnberg
Catherine H. Smith: King’s College London
Paola Di Meglio: King’s College London
Jonathan N. Barker: King’s College London
Lam C. Tsoi: University of Michigan Medical School
Michael A. Simpson: King’s College London
James T. Elder: University of Michigan Medical School

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci. To refine the genetic map of psoriasis susceptibility we meta-analysed 18 GWAS comprising 36,466 cases and 458,078 controls and identified 109 distinct psoriasis susceptibility loci, including 46 that have not been previously reported. These include susceptibility variants at loci in which the therapeutic targets IL17RA and AHR are encoded, and deleterious coding variants supporting potential new drug targets (including in STAP2, CPVL and POU2F3). We conducted a transcriptome-wide association study to identify regulatory effects of psoriasis susceptibility variants and cross-referenced these against single cell expression profiles in psoriasis-affected skin, highlighting roles for the transcriptional regulation of haematopoietic cell development and epigenetic modulation of interferon signalling in psoriasis pathobiology.

Date: 2025
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DOI: 10.1038/s41467-025-56719-8

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