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

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 S. 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; 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; A. David Burden; Sara J. Brown; Nick Dand; Satveer K. Mahil; Helen McAteer; Julia Schofield; Stefan Siebert; Andres Metspalu; Lili Milani; Mari Nelis; 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:10.1038/s41467-025-56719-8

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

P Philip E. Stuart J John Bowes D David Ellinghaus J Joanne Nititham J Jake R. Saklatvala M Maris Teder-Laving L Laurent F. Thomas T Tanel Traks S Steffen Uebe G Gunter Assmann D David Baudry F Frank Behrens A Allison C. Billi M Matthew A. Brown H Harald Burkhardt F Francesca Capon R Raymond Chung C Charles J. Curtis M Michael Duckworth E Eva Ellinghaus O Oliver FitzGerald S Sascha Gerdes C Christopher E. M. Griffiths S Susanne Gulliver P Philip S. Helliwell P Pauline Ho P Per Hoffmann O Oddgeir L. Holmen Z Zhi-ming Huang K Kristian Hveem D Deepak Jadon M Michaela Köhm C Cornelia Kraus C Céline Lamacchia S Sang Hyuck Lee F Feiyang Ma N Neil McHugh R Ross McManus E Ellen H. Modalsli M Michael J. Nissen M Markus Nöthen V Vinzenz Oji J Jorge R. Oksenberg M Matthew T. Patrick B Bethany E. Perez White A Andreas Ramming J Jürgen Rech (Friedrich Alexander Universität Erlangen–Nürnberg, Erlangen, Germany) C Cheryl Rosen M Mrinal K. Sarkar G Georg Schett (Friedrich-Alexander-Universität Erlangen–Nürnberg, Erlangen, Germany) B Börge Schmidt T Trilokraj Tejasvi H Heiko Traupe J John J. Voorhees E Eike Matthias Wacker R Richard B. Warren R Rachael Wasikowski S Stephan Weidinger X Xiaoquan Wen Z Zhaolin Zhang A A. David Burden S Sara J. Brown N Nick Dand S Satveer K. Mahil H Helen McAteer J Julia Schofield S Stefan Siebert A Andres Metspalu L Lili Milani M Mari Nelis A Anne Barton V Vinod Chandran T Tõnu Esko J John Foerster A Andre Franke D Dafna D. Gladman J Johann E. Gudjonsson W Wayne Gulliver U Ulrike Hüffmeier K Külli Kingo S Sulev Koks W Wilson Liao M Mari Løset R Reedik Mägi R Rajan P. Nair P Proton Rahman A André Reis C Catherine H. Smith P Paola Di Meglio J Jonathan N. Barker L Lam C. Tsoi M Michael A. Simpson J James T. Elder

Abstract

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.

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Article Details

Journal Nature Communications

Volume / Issue Vol. 16, Issue 1

Published February 28, 2025

DOI 10.1038/s41467-025-56719-8

ISSN 2041-1723

Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio

ISSN: 2041-1723 Open Access Life Sciences

Authors (93)

P

Philip E. Stuart

J

John Bowes

D

David Ellinghaus

J

Joanne Nititham

J

Jake R. Saklatvala

M

Maris Teder-Laving

L

Laurent F. Thomas

T

Tanel Traks

S

Steffen Uebe

G

Gunter Assmann

D

David Baudry

F

Frank Behrens

A

Allison C. Billi

M

Matthew A. Brown

H

Harald Burkhardt

F

Francesca Capon

R

Raymond Chung

C

Charles J. Curtis

M

Michael Duckworth

E

Eva Ellinghaus

O

Oliver FitzGerald

S

Sascha Gerdes

C

Christopher E. M. Griffiths

S

Susanne Gulliver

P

Philip S. Helliwell

P

Pauline Ho

P

Per Hoffmann

O

Oddgeir L. Holmen

Z

Zhi-ming Huang

K

Kristian Hveem

D

Deepak Jadon

M

Michaela Köhm

C

Cornelia Kraus

C

Céline Lamacchia

S

Sang Hyuck Lee

F

Feiyang Ma

N

Neil McHugh

R

Ross McManus

E

Ellen H. Modalsli

M

Michael J. Nissen

M

Markus Nöthen

V

Vinzenz Oji

J

Jorge R. Oksenberg

M

Matthew T. Patrick

B

Bethany E. Perez White

A

Andreas Ramming

J

Jürgen Rech

Friedrich Alexander Universität Erlangen–Nürnberg, Erlangen, Germany

C

Cheryl Rosen

M

Mrinal K. Sarkar

G

Georg Schett

Friedrich-Alexander-Universität Erlangen–Nürnberg, Erlangen, Germany

B

Börge Schmidt

T

Trilokraj Tejasvi

H

Heiko Traupe

J

John J. Voorhees

E

Eike Matthias Wacker

R

Richard B. Warren

R

Rachael Wasikowski

S

Stephan Weidinger

X

Xiaoquan Wen

Z

Zhaolin Zhang

A

A. David Burden

S

Sara J. Brown

N

Nick Dand

S

Satveer K. Mahil

H

Helen McAteer

J

Julia Schofield

S

Stefan Siebert

A

Andres Metspalu

L

Lili Milani

M

Mari Nelis

A

Anne Barton

V

Vinod Chandran

T

Tõnu Esko

J

John Foerster

A

Andre Franke

D

Dafna D. Gladman

J

Johann E. Gudjonsson

W

Wayne Gulliver

U

Ulrike Hüffmeier

K

Külli Kingo

S

Sulev Koks

W

Wilson Liao

M

Mari Løset

R

Reedik Mägi

R

Rajan P. Nair

P

Proton Rahman

A

André Reis

C

Catherine H. Smith

P

Paola Di Meglio

J

Jonathan N. Barker

L

Lam C. Tsoi

M

Michael A. Simpson

J

James T. Elder

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

Abstract

Article Details

Journal Info

Authors (93)

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