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

• DOI: 10.1101/2023.10.04.23296543
• Publication Date: 2023-10-06T00:13:07Z
• 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 G...; 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-W...; 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
• Keywords: Genome-wide Association Study

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 not fully explained variation at robustly risk loci. To move towards saturation map susceptibility we meta-analysed 18 GWAS comprising 36,466 cases and 458,078 controls 109 distinct loci, 45 that been previously reported. These include variants loci in which therapeutic targets IL17RA AHR are encoded, deleterious coding supporting potential new drug (including STAP2, CPVL POU2F3). We conducted transcriptome-wide association study identify regulatory effects cross-referenced these against single cell expression profiles psoriasis-affected skin, highlighting roles for transcriptional regulation haematopoietic development epigenetic modulation interferon signalling pathobiology.