Nature Communications (Feb 2025)
GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets
- 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 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,
- 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,
- 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 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
Affiliations
- Nick Dand
- Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London
- Philip E. Stuart
- Department of Dermatology, University of Michigan Medical School
- John Bowes
- Centre for Genetics and Genomics Versus Arthritis, The University of Manchester
- David Ellinghaus
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel
- Joanne Nititham
- Deparment of Dermatology, University of California San Francisco
- Jake R. Saklatvala
- Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London
- Maris Teder-Laving
- Institute of Genomics, University of Tartu
- Laurent F. Thomas
- Department of Clinical and Molecular Medicine, NTNU - Norwegian University of Science and Technology
- Tanel Traks
- Department of Dermatology and Venereology, Institute of Clinical Medicine, University of Tartu
- Steffen Uebe
- Institute of Human Genetics, Universitätsklinikum Erlangen, FAU Erlangen-Nürnberg
- Gunter Assmann
- RUB University Hospital JWK Minden, Department of Rheumatology
- David Baudry
- St John’s Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London
- Frank Behrens
- Division of Translational Rheumatology, Immunology - Inflammation Medicine, University Hospital, Goethe University
- Allison C. Billi
- Department of Dermatology, University of Michigan Medical School
- Matthew A. Brown
- Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London
- Harald Burkhardt
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
- Francesca Capon
- Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London
- Raymond Chung
- Institute of Psychiatry, Psychology and Neuroscience, King’s College London, Denmark Hill, Camberwell
- Charles J. Curtis
- Institute of Psychiatry, Psychology and Neuroscience, King’s College London, Denmark Hill, Camberwell
- Michael Duckworth
- St John’s Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London
- Eva Ellinghaus
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel
- Oliver FitzGerald
- UCD School of Medicine and Medical Sciences and Conway Institute of Biomolecular and Biomedical Research, University College Dublin
- Sascha Gerdes
- Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel
- Christopher E. M. Griffiths
- St John’s Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London
- Susanne Gulliver
- Newlab Clinical Research Inc
- Philip S. Helliwell
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds
- Pauline Ho
- Centre for Genetics and Genomics Versus Arthritis, The University of Manchester
- Per Hoffmann
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn
- Oddgeir L. Holmen
- HUNT Research Centre, Department of Public Health and Nursing, NTNU - Norwegian University of Science and Technology
- Zhi-ming Huang
- Deparment of Dermatology, University of California San Francisco
- Kristian Hveem
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU - Norwegian University of Science and Technology
- Deepak Jadon
- Department of Medicine, University of Cambridge
- Michaela Köhm
- Division of Translational Rheumatology, Immunology - Inflammation Medicine, University Hospital, Goethe University
- Cornelia Kraus
- Institute of Human Genetics, Universitätsklinikum Erlangen, FAU Erlangen-Nürnberg
- Céline Lamacchia
- Division of Rheumatology, Geneva University Hospital
- Sang Hyuck Lee
- Institute of Psychiatry, Psychology and Neuroscience, King’s College London, Denmark Hill, Camberwell
- Feiyang Ma
- Department of Dermatology, University of Michigan Medical School
- Satveer K. Mahil
- St John’s Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London
- Neil McHugh
- Department of Life Sciences, University of Bath
- Ross McManus
- Department of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College Dublin
- Ellen H. Modalsli
- Department of Clinical and Molecular Medicine, NTNU - Norwegian University of Science and Technology
- Michael J. Nissen
- Division of Rheumatology, Geneva University Hospital
- Markus Nöthen
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn
- Vinzenz Oji
- Department of Dermatology, University of Münster
- Jorge R. Oksenberg
- Weill Institute for Neurosciences, Department of Neurology, University of California
- Matthew T. Patrick
- Department of Dermatology, University of Michigan Medical School
- Bethany E. Perez White
- Department of Dermatology, Northwestern University
- Andreas Ramming
- Department of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
- Jürgen Rech
- Department of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
- Cheryl Rosen
- Division of Dermatology, Toronto Western Hospital, University of Toronto
- Mrinal K. Sarkar
- Department of Dermatology, University of Michigan Medical School
- Georg Schett
- Department of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
- Börge Schmidt
- Institute of Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen
- Trilokraj Tejasvi
- Department of Dermatology, University of Michigan Medical School
- Heiko Traupe
- Department of Dermatology, University of Münster
- John J. Voorhees
- Department of Dermatology, University of Michigan Medical School
- Eike Matthias Wacker
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel
- Richard B. Warren
- Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester
- Rachael Wasikowski
- Department of Dermatology, University of Michigan Medical School
- Stephan Weidinger
- Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel
- Xiaoquan Wen
- Department of Biostatistics, Center for Statistical Genetics, University of Michigan
- Zhaolin Zhang
- Department of Dermatology, University of Michigan Medical School
- BSTOP study group
- Estonian Biobank research team
- Anne Barton
- Centre for Genetics and Genomics Versus Arthritis, The University of Manchester
- Vinod Chandran
- Schroeder Arthritis Institute, Krembil Research Institute and Toronto Western Hospital, University Health Network and University of Toronto
- Tõnu Esko
- Institute of Genomics, University of Tartu
- John Foerster
- College of Medicine, Dentistry, and Nursing, University of Dundee
- Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel
- Dafna D. Gladman
- Schroeder Arthritis Institute, Krembil Research Institute and Toronto Western Hospital, University Health Network and University of Toronto
- Johann E. Gudjonsson
- Department of Dermatology, University of Michigan Medical School
- Wayne Gulliver
- Newlab Clinical Research Inc
- Ulrike Hüffmeier
- Institute of Human Genetics, Universitätsklinikum Erlangen, FAU Erlangen-Nürnberg
- Külli Kingo
- Department of Dermatology and Venereology, Institute of Clinical Medicine, University of Tartu
- Sulev Kõks
- Perron Institute for Neurological and Translational Science
- Wilson Liao
- Deparment of Dermatology, University of California San Francisco
- Mari Løset
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU - Norwegian University of Science and Technology
- Reedik Mägi
- Estonian Genome Centre, Institute of Genomics, University of Tartu
- Rajan P. Nair
- Department of Dermatology, University of Michigan Medical School
- Proton Rahman
- Memorial University of Newfoundland
- André Reis
- Institute of Human Genetics, Universitätsklinikum Erlangen, FAU Erlangen-Nürnberg
- Catherine H. Smith
- St John’s Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London
- Paola Di Meglio
- St John’s Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London
- Jonathan N. Barker
- St John’s Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London
- Lam C. Tsoi
- Department of Dermatology, University of Michigan Medical School
- Michael A. Simpson
- Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London
- James T. Elder
- Department of Dermatology, University of Michigan Medical School
- DOI
- https://doi.org/10.1038/s41467-025-56719-8
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 14
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.
