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

Nick Nand; Philip 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 M. Nöthen; Vinzenz Oji; Jorge Oksenberg; Matthew T. Patrick; Bethany E. Perez-White; Andreas Ramming; Jürgen Rech; Cheryl Rosen; Mrinal K. Sakar; 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; BSTOP study group; Estonian Biobank research team; Anne Barton; Vinod Chandran; Tõnu Esko; John Foerster; Andre Franke; Dafna D. Gladman; Johann E. Gudjonsson; Wayne Gulliver; Ulrike Hüffmeier; Külli Kingo; Sulev Koks; 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

doi:10.1101/2023.10.04.23296543

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

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

Nick Nand, Philip Stuart, John Bowes, David Ellinghaus, Joanne Nititham, Jake R. Saklatvala, Maris Teder-Laving, Laurent F. Thomas, Tanel Traks, Steffen Uebe, …

medRxiv

Cold Spring Habor Laboratory

DOI: https://doi.org/10.1101/2023.10.04.23296543

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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.

Details

Title: GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets
Authors/Creators: Nick Nand
Philip Stuart
John Bowes
David Ellinghaus
Joanne Nititham
Jake R. Saklatvala
Maris Teder-Laving
Laurent F. Thomas
Tanel Traks - University of Tartu
Steffen Uebe
Gunter Assmann
David Baudry
Frank Behrens
Allison C. Billi
Matthew A. Brown
Harald Burkhardt
Francesca Capon - King's College London
Raymond Chung
Charles J. Curtis
Michael Duckworth
Eva Ellinghaus
Oliver Fitzgerald
Sascha Gerdes
Christopher E. M. Griffiths - Manchester Academic Health Science Centre
Susanne Gulliver
Philip Helliwell
Pauline Ho
Per Hoffmann - University Hospital Bonn
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 - University of Bath
Ross McManus
Ellen H. Modalsli
Michael J. Nissen
Markus M. Nöthen - University Hospital Bonn
Vinzenz Oji
Jorge Oksenberg - University of California, San Francisco
Matthew T. Patrick
Bethany E. Perez-White
Andreas Ramming
Jürgen Rech
Cheryl Rosen
Mrinal K. Sakar
Georg Schett
Börge Schmidt
Trilokraj Tejasvi
Heiko Traupe
John J. Voorhees
Eike Matthias Wacker
Richard B. Warren - Manchester Academic Health Science Centre
Rachael Wasikowski
Stephan Weidinger - Christian-Albrechts-Universität zu Kiel
Xiaoquan Wen
Zhaolin Zhang
BSTOP study group
Estonian Biobank research team
Anne Barton
Vinod Chandran
Tõnu Esko
John Foerster
Andre Franke
Dafna D. Gladman
Johann E. Gudjonsson
Wayne Gulliver
Ulrike Hüffmeier
Külli Kingo - University of Tartu
Sulev Koks - Murdoch University, Centre for Molecular Medicine and Innovative Therapeutics
Wilson Liao
Mari Løset
Reedik Mägi
Rajan P. Nair
Proton Rahman
André Reis
Catherine H. Smith - King's College London
Paola Di Meglio
Jonathan N. Barker - King's College London
Lam C. Tsoi
Michael A. Simpson
James T. Elder
Publication Details: medRxiv
Publisher: Cold Spring Habor Laboratory
Identifiers: 991005610369807891
Copyright: The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
Murdoch Affiliation: Centre for Molecular Medicine and Innovative Therapeutics
Resource Type: Preprint

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