GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets.
Authors
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 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, James T 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.