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

Journal

medRxiv : the preprint server for health sciences
Titre abrégé: medRxiv
Pays: United States
ID NLM: 101767986

Informations de publication

Date de publication:
05 Oct 2023
Historique:
medline: 24 10 2023
pubmed: 24 10 2023
entrez: 24 10 2023
Statut: epublish

Résumé

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

Identifiants

DOI: 10.1101/2023.10.04.23296543 PMID: 37873414 PMC: PMC10593001
pubmed: 37873414
doi: 10.1101/2023.10.04.23296543
pmc: PMC10593001
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NIEHS NIH HHS
ID : R01 ES033634
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR042742
Pays : United States
Organisme : Medical Research Council
ID : MR/S003126/1
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : U01 AI119125
Pays : United States
Organisme : NIAMS NIH HHS
ID : K08 AR078251
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR075043
Pays : United States
Organisme : NIAMS NIH HHS
ID : K01 AR072129
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR054966
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR050511
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR065174
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM138121
Pays : United States
Organisme : NIAMS NIH HHS
ID : UC2 AR081033
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR065183
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR063611
Pays : United States

Déclaration de conflit d'intérêts

Conflicts of Interest FC reports grants and consultancy fees from Boehringer Ingelheim. SKM reports departmental income from Abbvie, Almirall, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi and UCB, outside the submitted work. MJN has received consultancy fees and/or research funding from Abbvie, Amgen, Celgene, Eli Lilly, Janssen, Pfizer, Novartis and UCB. T.Tejasvi is a member of an advisory board for L’Oreal Teledermatology. VC has received research grants from AbbVie, Amgen, and Eli Lilly and has received honoraria for advisory board member roles from AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. His spouse is an employee of AstraZeneca. JEG received research support from Eli Lilly, Kyowa Kirin, Janssen, Almirall, Celgene/BMS, Prometheus, Novartis, Galderma and AnaptysBio, and is a member of an advisory board for Novartis, AbbVie, Eli Lilly, Almirall, Galderma, Boehringer Ingelehim, Celgene/BMS, Sanofi, Janssen and AnaptysBio. SK is a founder of Prion OÜ, Geneto OÜ, Sportsgene OÜ and Genomic Therapeutics Pty Ltd. WL has received research grant funding from Abbvie, Amgen, Janssen, Leo, Novartis, Pfizer, Regeneron, and TRex Bio. PDM reports consultancy fees from Unilever and speaker’s fees from Sanofi and BMS. LCT reports support from Janssen, Galderma, and Novartis. The remaining authors report no conflicts of interest.

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Auteurs

Nick Dand (N)

Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.
Health Data Research UK, London, UK.

Philip E Stuart (PE)

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

John Bowes (J)

Centre for Genetics and Genomics Versus Arthritis, The University of Manchester, Manchester, UK.
National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre, The University of Manchester, Manchester, UK.

David Ellinghaus (D)

Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.

Joanne Nititham (J)

Deparment of Dermatology, University of California San Francisco, San Francisco, CA, USA.

Jake R Saklatvala (JR)

Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.

Maris Teder-Laving (M)

Institute of Genomics, University of Tartu, Tartu, Estonia.

Laurent F Thomas (LF)

Department of Clinical and Molecular Medicine, NTNU - Norwegian University of Science and Technology, Trondheim, Norway.
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU - Norwegian University of Science and Technology, Trondheim, Norway.
BioCore - Bioinformatics Core Facility, NTNU - Norwegian University of Science and Technology, Trondheim, Norway.
Clinic of Laboratory Medicine, St.Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Tanel Traks (T)

Department of Dermatology and Venereology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.

Steffen Uebe (S)

Institute of Human Genetics, Universitätsklinikum Erlangen, FAU Erlangen-Nürnberg, Erlangen, Germany.

Gunter Assmann (G)

RUB University Hospital JWK Minden, Department of Rheumatology, Minden, Germany.
Jose-Carreras Centrum for Immuno- and Gene Therapy, University of Saarland Medical School, Homburg, Germany.

David Baudry (D)

St John's Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.

Frank Behrens (F)

Division of Translational Rheumatology, Immunology - Inflammation Medicine, University Hospital, Goethe University, Frankfurt am Main, Germany.
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany.
Fraunhofer Cluster of Excellence Immune-mediated Diseases CIMD, Frankfurt am Main, Germany.
Division of Rheumatology, University Hospital, Goethe University, Frankfurt am Main, Germany.

Allison C Billi (AC)

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Matthew A Brown (MA)

Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.
Genomics England, Canary Wharf, London, UK.

Harald Burkhardt (H)

Division of Rheumatology, University Hospital, Goethe University, Frankfurt am Main, Germany.
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany.
Fraunhofer Cluster of Excellence Immune-mediated Diseases CIMD, Frankfurt am Main, Germany.

Francesca Capon (F)

Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.

Raymond Chung (R)

Institute of Psychiatry, Psychology and Neuroscience, King's College London, Denmark Hill, Camberwell, London, UK.
National Institute for Health and Care Research (NIHR) Biomedical Research Centre, South London and Maudsley Hospital, London, UK.

Charles J Curtis (CJ)

Institute of Psychiatry, Psychology and Neuroscience, King's College London, Denmark Hill, Camberwell, London, UK.
National Institute for Health and Care Research (NIHR) Biomedical Research Centre, South London and Maudsley Hospital, London, UK.

Michael Duckworth (M)

St John's Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.

Eva Ellinghaus (E)

Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.

Oliver FitzGerald (O)

UCD School of Medicine and Medical Sciences and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland.

Sascha Gerdes (S)

Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Christopher E M Griffiths (CEM)

Centre for Dermatology Research, University of Manchester, NIHR Manchester Biomedical Research Centre, Manchester, UK.
St John's Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.
Department of Dermatology, King's College Hospital NHS Foundation Trust, London, UK.

Susanne Gulliver (S)

Newlab Clinical Research Inc, St. John's, NL, Canada.

Philip Helliwell (P)

National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust, UK.
Leeds Institute of Rheumatic and Musculoskeletal Disease, University of Leeds, UK.

Pauline Ho (P)

Centre for Genetics and Genomics Versus Arthritis, The University of Manchester, Manchester, UK.
National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre, The University of Manchester, Manchester, UK.
The Kellgren Centre for Rheumatology, Manchester University NHS Foundation Trust, Manchester, UK.

Per Hoffmann (P)

Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.

Oddgeir L Holmen (OL)

HUNT Research Centre, Department of Public Health and Nursing, NTNU - Norwegian University of Science and Technology, Levanger, Norway.
Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.

Zhi-Ming Huang (ZM)

Deparment of Dermatology, University of California San Francisco, San Francisco, CA, USA.

Kristian Hveem (K)

K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU - Norwegian University of Science and Technology, Trondheim, Norway.
HUNT Research Centre, Department of Public Health and Nursing, NTNU - Norwegian University of Science and Technology, Levanger, Norway.
Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.

Deepak Jadon (D)

Department of Medicine, University of Cambridge, Cambridge, UK.

Michaela Köhm (M)

Division of Translational Rheumatology, Immunology - Inflammation Medicine, University Hospital, Goethe University, Frankfurt am Main, Germany.
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany.
Fraunhofer Cluster of Excellence Immune-mediated Diseases CIMD, Frankfurt am Main, Germany.
Division of Rheumatology, University Hospital, Goethe University, Frankfurt am Main, Germany.

Cornelia Kraus (C)

Institute of Human Genetics, Universitätsklinikum Erlangen, FAU Erlangen-Nürnberg, Erlangen, Germany.

Céline Lamacchia (C)

Division of Rheumatology, Geneva University Hospital, Geneva, Switzerland.

Sang Hyuck Lee (SH)

Institute of Psychiatry, Psychology and Neuroscience, King's College London, Denmark Hill, Camberwell, London, UK.
National Institute for Health and Care Research (NIHR) Biomedical Research Centre, South London and Maudsley Hospital, London, UK.

Feiyang Ma (F)

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.

Satveer K Mahil (SK)

St John's Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.
St John's Institute of Dermatology, Guy's and St Thomas' National Health Service (NHS) Foundation Trust, London, UK.

Neil McHugh (N)

Royal National Hospital for Rheumatic Diseases and Dept Pharmacy and Pharmacology, University of Bath, UK.

Ross McManus (R)

Department of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Ireland.

Ellen H Modalsli (EH)

Department of Clinical and Molecular Medicine, NTNU - Norwegian University of Science and Technology, Trondheim, Norway.
Department of Dermatology, Clinic of Orthopedy, Rheumatology and Dermatology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Michael J Nissen (MJ)

Division of Rheumatology, Geneva University Hospital, Geneva, Switzerland.

Markus Nöthen (M)

Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.

Vinzenz Oji (V)

Department of Dermatology, University of Münster, Münster, Germany.

Jorge R Oksenberg (JR)

Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA.

Matthew T Patrick (MT)

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Bethany E Perez-White (BE)

Department of Dermatology, Northwestern University, Evanston, IL, USA.

Andreas Ramming (A)

Department of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Ulmenweg 18, 91054, Erlangen, Germany.
Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.

Jürgen Rech (J)

Department of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Ulmenweg 18, 91054, Erlangen, Germany.
Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.

Cheryl Rosen (C)

Division of Dermatology, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.

Mrinal K Sarkar (MK)

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Georg Schett (G)

Department of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Ulmenweg 18, 91054, Erlangen, Germany.
Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.

Börge Schmidt (B)

Institute of Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Trilokraj Tejasvi (T)

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.
Ann Arbor Veterans Affairs Hospital, Ann Arbor, MI, USA.

Heiko Traupe (H)

Department of Dermatology, University of Münster, Münster, Germany.

John J Voorhees (JJ)

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Eike Matthias Wacker (EM)

Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.

Richard B Warren (RB)

Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, UK.
Centre for Dermatology Research, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M6 8HD, UK.

Rachael Wasikowski (R)

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Stephan Weidinger (S)

Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Xiaoquan Wen (X)

Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.

Zhaolin Zhang (Z)

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Anne Barton (A)

Centre for Genetics and Genomics Versus Arthritis, The University of Manchester, Manchester, UK.
National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre, The University of Manchester, Manchester, UK.
The Kellgren Centre for Rheumatology, Manchester University NHS Foundation Trust, Manchester, UK.

Vinod Chandran (V)

Schroeder Arthritis Institute, Krembil Research Institute, and Toronto Western Hospital, University Health Network and University of Toronto, Toronto, Ontario, Canada.

Tõnu Esko (T)

Institute of Genomics, University of Tartu, Tartu, Estonia.

John Foerster (J)

College of Medicine, Dentistry, and Nursing, University of Dundee, Dundee, UK.

Andre Franke (A)

Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.

Dafna D Gladman (DD)

Schroeder Arthritis Institute, Krembil Research Institute, and Toronto Western Hospital, University Health Network and University of Toronto, Toronto, Ontario, Canada.

Johann E Gudjonsson (JE)

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Wayne Gulliver (W)

Newlab Clinical Research Inc, St. John's, NL, Canada.
Department of Dermatology, Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.

Ulrike Hüffmeier (U)

Institute of Human Genetics, Universitätsklinikum Erlangen, FAU Erlangen-Nürnberg, Erlangen, Germany.

Külli Kingo (K)

Department of Dermatology and Venereology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
Dermatology Clinic, Tartu University Hospital, Tartu, Estonia.

Sulev Kõks (S)

Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia.
Centre for Molecular Medicine and Innovative Therapeutics, Health Futures Institute, Murdoch University, Perth, WA 6150, Australia.

Wilson Liao (W)

Deparment of Dermatology, University of California San Francisco, San Francisco, CA, USA.

Mari Løset (M)

K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU - Norwegian University of Science and Technology, Trondheim, Norway.
Department of Dermatology, Clinic of Orthopedy, Rheumatology and Dermatology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Reedik Mägi (R)

Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.

Rajan P Nair (RP)

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.

Proton Rahman (P)

Memorial University of Newfoundland, St. John's, NL, Canada.

André Reis (A)

Institute of Human Genetics, Universitätsklinikum Erlangen, FAU Erlangen-Nürnberg, Erlangen, Germany.

Catherine H Smith (CH)

St John's Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.
St John's Institute of Dermatology, Guy's and St Thomas' National Health Service (NHS) Foundation Trust, London, UK.

Paola Di Meglio (P)

St John's Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.

Jonathan N Barker (JN)

St John's Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.
St John's Institute of Dermatology, Guy's and St Thomas' National Health Service (NHS) Foundation Trust, London, UK.

Lam C Tsoi (LC)

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.

Michael A Simpson (MA)

Department of Medical & Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.

James T Elder (JT)

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.
Ann Arbor Veterans Affairs Hospital, Ann Arbor, MI, USA.

Classifications MeSH