GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets
Authors
Nick Dand, Philip Stuart, John Bowes, David Ellinghaus, Joanne Nititham, Jake Saklatvala, Maris Teder-Laving, Laurent Thomas, Tanel Traks, Steffen Uebe, Gunter Assmann, David Baudry, Frank Behrens, Allison Billi, Matthew Brown, Harald Burkhardt, Francesca Capon, Raymond Chung, Charles Curtis, Michael Duckworth, Eva Ellinghaus, Oliver FitzGerald, Sascha Gerdes, Christopher Griffiths, Susanne Gulliver, Philip Helliwell, Pauline Ho, Per Hoffmann, Oddgeir Holmen, Zhi-ming Huang, Kristian Hveem, Deepak Jadon, Michaela Köhm, Cornelia Kraus, Céline Lamacchia, Sang Hyuck Lee, Feiyang Ma, Satveer Mahil, Neil McHugh, Ross McManus, Ellen Modalsli, Michael Nissen, Markus Nöthen, Vinzenz Oji, Jorge Oksenberg, Matthew Patrick, Bethany Perez-White, Andreas Ramming, Jürgen Rech, Cheryl Rosen, Mrinal Sarkar, Georg Schett, Börge Schmidt, Trilokraj Tejasvi, Heiko Traupe, John Voorhees, Eike Matthias Wacker, Richard Warren, Rachael Wasikowski, Stephan Weidinger, Xiaoquan Wen, Zhaolin Zhang, Anne Barton, Vinod Chandran, Tõnu Esko, John Foerster, Andre Franke, Dafna Gladman, Johann Gudjonsson, Wayne Gulliver, Ulrike Hüffmeier, Külli Kingo, Sulev Kõks, Wilson Liao, Mari Løset, Reedik Mägi, Rajan Nair, Proton Rahman, André Reis, Catherine Smith, Paola Di Meglio, Jonathan Barker, Lam Tsoi, Michael Simpson, James Elder
Year of publication
2023Journal
UKNVolume
-Issue
-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 move towards a saturation 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 45 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.