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

Dand N, Stuart PE, Bowes J, Ellinghaus D, Nititham J, Saklatvala JR, Teder-Laving M, Thomas LF, Traks T, Uebe S, Assmann G, Baudry D, Behrens F, Billi AC, Brown MA, Burkhardt H, Capon F, Chung R, Curtis CJ, Duckworth M, Ellinghaus E, FitzGerald O, Gerdes S, Griffiths CE, Gulliver S, Helliwell PS, Ho P, Hoffmann P, Holmen OL, Huang ZM, Hveem K, Jadon D, Köhm M, Kraus C, Lamacchia C, Lee SH, Ma F, Mahil SK, McHugh N, McManus R, Modalsli EH, Nissen MJ, Nöthen M, Oji V, Oksenberg JR, Patrick MT, Perez White BE, Ramming A, Rech J, Rosen C, Sarkar MK, Schett G, Schmidt B, Tejasvi T, Traupe H, Voorhees JJ, Wacker EM, Warren RB, Wasikowski R, Weidinger S, Wen X, Zhang Z, Burden AD, Smith CH, Brown SJ, Mahil SK, McAteer H, Schofield J, Siebert S, Metspalu A, Milani L, Nelis M, Barton A, Chandran V, Esko T, Foerster J, Franke A, Gladman DD, Gudjonsson JE, Gulliver W, Hüffmeier U, Kingo K, Kõks S, Liao W, Løset M, Mägi R, Nair RP, Rahman P, Reis A, Di Meglio P, Barker JN, Tsoi LC, Simpson MA, Elder JT (2025)

Publication Language: English

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 16

Article Number: 2051

Journal Issue: 1

DOI: 10.1038/s41467-025-56719-8

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.

Authors with CRIS profile

Involved external institutions

University of Michigan United States (USA) (US) Christian-Albrechts-Universität zu Kiel Germany (DE) King’s College London United Kingdom (GB) University of Manchester United Kingdom (GB) Psoriasis Association United Kingdom (GB) Trinity College Dublin Ireland (IE) NTNU Trondheim - Norwegian University of Science and Technology Norway (NO) University of California San Francisco (UCSF) United States (USA) (US) Universitätsklinikum Bonn Germany (DE) Johannes Wesling Klinikum Minden Germany (DE) Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG) Switzerland (CH) University of Glasgow United Kingdom (GB) University College Dublin (UCD) Ireland (IE) University of Tartu Estonia (EE) University of Edinburgh United Kingdom (GB) Perron Institute for Neurological and Translational Science Australia (AU) University of Cambridge United Kingdom (GB) University Health Network (UHN) Canada (CA) University of Leeds United Kingdom (GB) University of Dundee United Kingdom (GB) Northwestern University United States (USA) (US) Toronto Western Hospital Canada (CA) Newlab Clinical Research Inc Canada (CA) Memorial University of Newfoundland (MUN) Canada (CA) Westfälische Wilhelms-Universität (WWU) Münster Germany (DE) Fraunhofer-Institut für Translationale Medizin und Pharmakologie (ITMP) / Fraunhofer Institute for Translational Medicine and Pharmacology Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) University of Bath United Kingdom (GB) Guy's and St Thomas' (NHS Foundation Trust) United Kingdom (GB) Universitätsklinikum Essen Germany (DE)

How to cite

APA:

Dand, N., Stuart, P.E., Bowes, J., Ellinghaus, D., Nititham, J., Saklatvala, J.R.,... Elder, J.T. (2025). GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets. Nature Communications, 16(1). https://doi.org/10.1038/s41467-025-56719-8

MLA:

Dand, Nick, et al. "GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets." Nature Communications 16.1 (2025).

BibTeX: Download