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European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

Author

Listed:
  • Ashley Budu-Aggrey

    (University of Bristol
    University of Bristol)

  • Anna Kilanowski

    (Helmholtz Zentrum München - German Research Center for Environmental Health
    University of Munich Medical Center
    Ludwig-Maximilians University Munich)

  • Maria K. Sobczyk

    (University of Bristol
    University of Bristol)

  • Suyash S. Shringarpure

    (23andMe, Inc.)

  • Ruth Mitchell

    (University of Bristol
    University of Bristol)

  • Kadri Reis

    (University of Tartu)

  • Anu Reigo

    (University of Tartu)

  • Reedik Mägi

    (University of Tartu)

  • Mari Nelis

    (University of Tartu
    University of Tartu)

  • Nao Tanaka

    (RIKEN Center for Integrative Medical Sciences
    Tokyo Medical and Dental University (TMDU))

  • Ben M. Brumpton

    (Norwegian University of Science and Technology
    Norwegian University of Science and Technology
    Trondheim University Hospital)

  • Laurent F. Thomas

    (Norwegian University of Science and Technology
    NTNU Norwegian University of Science and Technology
    Norwegian University of Science and Technology
    Trondheim University Hospital)

  • Pol Sole-Navais

    (University of Gothenburg)

  • Christopher Flatley

    (University of Gothenburg)

  • Antonio Espuela-Ortiz

    (Universidad de La Laguna)

  • Esther Herrera-Luis

    (Universidad de La Laguna)

  • Jesus V. T. Lominchar

    (University of Copenhagen)

  • Jette Bork-Jensen

    (University of Copenhagen)

  • Ingo Marenholz

    (Max-Delbrück-Center for Molecular Medicine
    Charité-Universitätsmedizin Berlin)

  • Aleix Arnau-Soler

    (Max-Delbrück-Center for Molecular Medicine
    Charité-Universitätsmedizin Berlin)

  • Ayoung Jeong

    (Swiss Tropical and Public Health Institute
    University of Basel)

  • Katherine A. Fawcett

    (University of Leicester)

  • Hansjorg Baurecht

    (University of Regensburg)

  • Elke Rodriguez

    (University Hospital Schleswig-Holstein)

  • Alexessander Couto Alves

    (University of Surrey)

  • Ashish Kumar

    (Karolinska Institutet)

  • Patrick M. Sleiman

    (Children’s Hospital of Philadelphia
    University of Pennsylvania
    Rhythm Pharmaceuticals)

  • Xiao Chang

    (Children’s Hospital of Philadelphia)

  • Carolina Medina-Gomez

    (University Medical Center Rotterdam
    University Medical Center Rotterdam)

  • Chen Hu

    (University Medical Center Rotterdam
    University Medical Center Rotterdam)

  • Cheng-jian Xu

    (University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children’s Hospital
    University of Groningen, University Medical Center Groningen, GRIAC Research Institute
    CiiM, a joint venture between Hannover Medical School and the Helmholtz Centre for Infection Research
    Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research)

  • Cancan Qi

    (University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children’s Hospital
    University of Groningen, University Medical Center Groningen, GRIAC Research Institute)

  • Sarah El-Heis

    (University of Southampton)

  • Philip Titcombe

    (University of Southampton)

  • Elie Antoun

    (University of Southampton
    University of Southampton)

  • João Fadista

    (Department of Bioinformatics & Data Mining
    Statens Serum Institut
    Lund University Diabetes Centre
    University of Helsinki)

  • Carol A. Wang

    (University of Newcastle
    Hunter Medical Research Institute)

  • Elisabeth Thiering

    (Helmholtz Zentrum München - German Research Center for Environmental Health
    University of Munich Medical Center)

  • Baojun Wu

    (Henry Ford Health)

  • Sara Kress

    (Brain and Skin Aging, IUF – Leibniz Research Institute for Environmental Medicine)

  • Dilini M. Kothalawala

    (University of Southampton
    University Hospital Southampton)

  • Latha Kadalayil

    (University of Southampton)

  • Jiasong Duan

    (University of Memphis)

  • Hongmei Zhang

    (University of Memphis)

  • Sabelo Hadebe

    (University of Cape Town)

  • Thomas Hoffmann

    (Institute for Human Genetics, UCSF
    UCSF)

  • Eric Jorgenson

    (Regeneron Genetics Center)

  • Hélène Choquet

    (Kaiser Permanente Northern California)

  • Neil Risch

    (Institute for Human Genetics, UCSF
    UCSF)

  • Pål Njølstad

    (University of Bergen
    Haukeland University Hospital)

  • Ole A. Andreassen

    (University of Oslo
    Oslo University Hospital)

  • Stefan Johansson

    (University of Bergen
    Haukeland University Hospital)

  • Catarina Almqvist

    (Karolinska Institutet
    Karolinska University Hospital)

  • Tong Gong

    (Karolinska Institutet)

  • Vilhelmina Ullemar

    (Karolinska Institutet)

  • Robert Karlsson

    (Karolinska Institutet)

  • Patrik K. E. Magnusson

    (Karolinska Institutet)

  • Agnieszka Szwajda

    (Karolinska Institutet)

  • Esteban G. Burchard

    (University of California San Francisco
    University of California San Francisco)

  • Jacob P. Thyssen

    (University of Copenhagen)

  • Torben Hansen

    (University of Copenhagen)

  • Line L. Kårhus

    (Bispebjerg and Frederiksberg Hospital)

  • Thomas M. Dantoft

    (Bispebjerg and Frederiksberg Hospital)

  • Alexander C.S.N. Jeanrenaud

    (Max-Delbrück-Center for Molecular Medicine
    Charité-Universitätsmedizin Berlin)

  • Ahla Ghauri

    (Max-Delbrück-Center for Molecular Medicine
    Charité-Universitätsmedizin Berlin)

  • Andreas Arnold

    (University Medicine Greifswald)

  • Georg Homuth

    (University Medicine Greifswald)

  • Susanne Lau

    (Charité-Universitätsmedizin Berlin)

  • Markus M. Nöthen

    (University of Bonn, School of Medicine & University Hospital Bonn)

  • Norbert Hübner

    (Max-Delbrück-Center for Molecular Medicine
    Charite-Universitätsmedizin Berlin)

  • Medea Imboden

    (Swiss Tropical and Public Health Institute
    University of Basel)

  • Alessia Visconti

    (Kings College London)

  • Mario Falchi

    (Kings College London)

  • Veronique Bataille

    (Kings College London
    West Herts NHS Trust)

  • Pirro Hysi

    (Kings College London)

  • Natalia Ballardini

    (Karolinska Institutet)

  • Dorret I. Boomsma

    (VU University
    VU University)

  • Jouke J. Hottenga

    (VU University)

  • Martina Müller-Nurasyid

    (Helmholtz Zentrum München - German Research Center for Environmental Health
    LMU Munich
    University Medical Center, Johannes Gutenberg University)

  • Tarunveer S. Ahluwalia

    (University of Copenhagen
    Steno Diabetes Center Copenhagen
    University of Copenhagen)

  • Jakob Stokholm

    (University of Copenhagen
    Slagelse Hospital)

  • Bo Chawes

    (University of Copenhagen)

  • Ann-Marie M. Schoos

    (University of Copenhagen
    Slagelse Hospital)

  • Ana Esplugues

    (University of Valencia, FISABIO-University Jaume I-University of Valencia
    Joint Research Unit of Epidemiology and Environmental Health, CIBERESP)

  • Mariona Bustamante

    (ISGlobal, Institute for Global Health
    Universitat Pompeu Fabra (UPF)
    CIBER Epidemiología y Salud Pública)

  • Benjamin Raby

    (Brigham & Women’s Hospital and Harvard Medical School)

  • Syed Arshad

    (University of Southampton
    David Hide Asthma and Allergy Research Centre)

  • Chris German

    (23andMe, Inc.)

  • Tõnu Esko

    (University of Tartu)

  • Lili A. Milani

    (University of Tartu)

  • Andres Metspalu

    (University of Tartu)

  • Chikashi Terao

    (RIKEN Center for Integrative Medical Sciences
    Clinical Research Center, Shizuoka General Hospital
    University of Shizuoka)

  • Katrina Abuabara

    (University of California San Francisco)

  • Mari Løset

    (Norwegian University of Science and Technology
    Trondheim University Hospital)

  • Kristian Hveem

    (Norwegian University of Science and Technology
    Norwegian University of Science and Technology)

  • Bo Jacobsson

    (University of Gothenburg
    Norwegian Institute of Public Health)

  • Maria Pino-Yanes

    (Universidad de La Laguna
    Instituto de Salud Carlos III
    Universidad de La Laguna, San Cristóbal de La Laguna)

  • David P. Strachan

    (University of London, Cranmer Terrace)

  • Niels Grarup

    (University of Copenhagen)

  • Allan Linneberg

    (Bispebjerg and Frederiksberg Hospital
    University of Copenhagen)

  • Young-Ae Lee

    (Max-Delbrück-Center for Molecular Medicine
    Charité-Universitätsmedizin Berlin)

  • Nicole Probst-Hensch

    (Swiss Tropical and Public Health Institute
    University of Basel)

  • Stephan Weidinger

    (University Hospital Schleswig-Holstein)

  • Marjo-Riitta Jarvelin

    (School of Public Health,Imperial College London
    University of Oulu
    University of Oulu)

  • Erik Melén

    (Karolinska Institutet)

  • Hakon Hakonarson

    (Children’s Hospital of Philadelphia
    University of Pennsylvania
    University of Iceland)

  • Alan D. Irvine

    (Trinity College)

  • Deborah Jarvis

    (Imperial College London
    Medical Research Council and Public Health England Centre for Environment and Health)

  • Tamar Nijsten

    (University Medical Center Rotterdam)

  • Liesbeth Duijts

    (University Medical Center Rotterdam
    University Medical Center Rotterdam)

  • Judith M. Vonk

    (University of Groningen, University Medical Center Groningen, GRIAC Research Institute
    University of Groningen, University Medical Center Groningen, Department of Epidemiology)

  • Gerard H. Koppelmann

    (University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children’s Hospital
    University of Groningen, University Medical Center Groningen, GRIAC Research Institute)

  • Keith M. Godfrey

    (University of Southampton and University Hospital Southampton NHS Foundation Trust)

  • Sheila J. Barton

    (University of Southampton)

  • Bjarke Feenstra

    (Statens Serum Institut)

  • Craig E. Pennell

    (University of Newcastle
    Hunter Medical Research Institute)

  • Peter D. Sly

    (The University of Queensland
    The University of Queensland)

  • Patrick G. Holt

    (University of Western Australia)

  • L. Keoki Williams

    (Henry Ford Health)

  • Hans Bisgaard

    (University of Copenhagen)

  • Klaus Bønnelykke

    (University of Copenhagen)

  • John Curtin

    (The University of Manchester, Manchester Academic Health Science Centre, and Manchester University NHS Foundation Trust)

  • Angela Simpson

    (The University of Manchester, Manchester Academic Health Science Centre, and Manchester University NHS Foundation Trust)

  • Clare Murray

    (The University of Manchester, Manchester Academic Health Science Centre, and Manchester University NHS Foundation Trust)

  • Tamara Schikowski

    (Leibniz Research Institute for Environmental Medicine)

  • Supinda Bunyavanich

    (Icahn School of Medicine at Mount Sinai)

  • Scott T. Weiss

    (Brigham & Women’s Hospital and Harvard Medical School)

  • John W. Holloway

    (University of Southampton
    University of Southampton)

  • Josine L. Min

    (University of Bristol
    University of Bristol)

  • Sara J. Brown

    (University of Edinburgh)

  • Marie Standl

    (Helmholtz Zentrum München - German Research Center for Environmental Health
    German Center for Lung Research (DZL))

  • Lavinia Paternoster

    (University of Bristol
    University of Bristol)

Abstract

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.

Suggested Citation

  • Ashley Budu-Aggrey & Anna Kilanowski & Maria K. Sobczyk & Suyash S. Shringarpure & Ruth Mitchell & Kadri Reis & Anu Reigo & Reedik Mägi & Mari Nelis & Nao Tanaka & Ben M. Brumpton & Laurent F. Thomas , 2023. "European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41180-2
    DOI: 10.1038/s41467-023-41180-2
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