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

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, Pol Sole-Navais, Christopher Flatley, Antonio Espuela-Ortiz, Esther Herrera-Luis, Jesus V. T. Lominchar, Jette Bork-Jensen, Ingo Marenholz, Aleix Arnau-Soler, Ayoung Jeong, Katherine A. Fawcett, Hansjorg Baurecht, Elke Rodriguez, Alexessander Couto Alves, Ashish Kumar, Patrick M. Sleiman, Xiao Chang, Carolina Medina-Gomez, Chen Hu, Cheng-jian Xu, Cancan Qi, Sarah El-Heis, Philip Titcombe, Elie Antoun, João Fadista, Carol A. Wang, Elisabeth Thiering, Baojun Wu, Sara Kress, Dilini M. Kothalawala, Latha Kadalayil, Jiasong Duan, Hongmei Zhang, Sabelo Hadebe, Thomas Hoffmann, Eric Jorgenson, Hélène Choquet, Neil Risch, Pål Njølstad, Ole A. Andreassen, Stefan Johansson, Catarina Almqvist, Tong Gong, Vilhelmina Ullemar, Robert Karlsson, Patrik K. E. Magnusson, Agnieszka Szwajda, Esteban G. Burchard, Jacob P. Thyssen, Torben Hansen, Line L. Kårhus, Thomas M. Dantoft, Alexander C.S.N. Jeanrenaud, Ahla Ghauri, Andreas Arnold, Georg Homuth, Susanne Lau, Markus M. Nöthen, Norbert Hübner, Medea Imboden, Alessia Visconti, Mario Falchi, Veronique Bataille, Pirro Hysi, Natalia Ballardini, Dorret I. Boomsma, Jouke J. Hottenga, Martina Müller-Nurasyid, Tarunveer S. Ahluwalia, Jakob Stokholm, Bo Chawes, Ann-Marie M. Schoos, Ana Esplugues, Mariona Bustamante, Benjamin Raby, Syed Arshad, Chris German, Tõnu Esko, Lili A. Milani, Andres Metspalu, Chikashi Terao, Katrina Abuabara, Mari Løset, Kristian Hveem, Bo Jacobsson, Maria Pino-Yanes, David P. Strachan, Niels Grarup, Allan Linneberg, Young-Ae Lee, Nicole Probst-Hensch, Stephan Weidinger, Marjo-Riitta Jarvelin, Erik Melén, Hakon Hakonarson, Alan D. Irvine, Deborah Jarvis, Tamar Nijsten, Liesbeth Duijts, Judith M. Vonk, Gerard H. Koppelmann, Keith M. Godfrey, Sheila J. Barton, Bjarke Feenstra, Craig E. Pennell, Peter D. Sly, Patrick G. Holt, L. Keoki Williams, Hans Bisgaard, Klaus Bønnelykke, John Curtin, Angela Simpson, Clare Murray, Tamara Schikowski, Supinda Bunyavanich, Scott T. Weiss, John W. Holloway, Josine L. Min, Sara J. Brown, Marie Standl and Lavinia Paternoster ()
Additional contact information
Ashley Budu-Aggrey: University of Bristol
Anna Kilanowski: Helmholtz Zentrum München - German Research Center for Environmental Health
Maria K. Sobczyk: University of Bristol
Suyash S. Shringarpure: 23andMe, Inc.
Ruth Mitchell: University of Bristol
Kadri Reis: University of Tartu
Anu Reigo: University of Tartu
Reedik Mägi: University of Tartu
Mari Nelis: University of Tartu
Nao Tanaka: RIKEN Center for Integrative Medical Sciences
Ben M. Brumpton: Norwegian University of Science and Technology
Laurent F. Thomas: Norwegian University of Science and Technology
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
Aleix Arnau-Soler: Max-Delbrück-Center for Molecular Medicine
Ayoung Jeong: Swiss Tropical and Public Health Institute
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
Xiao Chang: Children’s Hospital of Philadelphia
Carolina Medina-Gomez: University Medical Center Rotterdam
Chen Hu: 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
Cancan Qi: University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children’s Hospital
Sarah El-Heis: University of Southampton
Philip Titcombe: University of Southampton
Elie Antoun: University of Southampton
João Fadista: Department of Bioinformatics & Data Mining
Carol A. Wang: University of Newcastle
Elisabeth Thiering: Helmholtz Zentrum München - German Research Center for Environmental Health
Baojun Wu: Henry Ford Health
Sara Kress: Brain and Skin Aging, IUF – Leibniz Research Institute for Environmental Medicine
Dilini M. Kothalawala: University of 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
Eric Jorgenson: Regeneron Genetics Center
Hélène Choquet: Kaiser Permanente Northern California
Neil Risch: Institute for Human Genetics, UCSF
Pål Njølstad: University of Bergen
Ole A. Andreassen: University of Oslo
Stefan Johansson: University of Bergen
Catarina Almqvist: Karolinska Institutet
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
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
Ahla Ghauri: Max-Delbrück-Center for Molecular Medicine
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
Medea Imboden: Swiss Tropical and Public Health Institute
Alessia Visconti: Kings College London
Mario Falchi: Kings College London
Veronique Bataille: Kings College London
Pirro Hysi: Kings College London
Natalia Ballardini: Karolinska Institutet
Dorret I. Boomsma: VU University
Jouke J. Hottenga: VU University
Martina Müller-Nurasyid: Helmholtz Zentrum München - German Research Center for Environmental Health
Tarunveer S. Ahluwalia: University of Copenhagen
Jakob Stokholm: University of Copenhagen
Bo Chawes: University of Copenhagen
Ann-Marie M. Schoos: University of Copenhagen
Ana Esplugues: University of Valencia, FISABIO-University Jaume I-University of Valencia
Mariona Bustamante: ISGlobal, Institute for Global Health
Benjamin Raby: Brigham & Women’s Hospital and Harvard Medical School
Syed Arshad: University of Southampton
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
Katrina Abuabara: University of California San Francisco
Mari Løset: Norwegian University of Science and Technology
Kristian Hveem: Norwegian University of Science and Technology
Bo Jacobsson: University of Gothenburg
Maria Pino-Yanes: Universidad de La Laguna
David P. Strachan: University of London, Cranmer Terrace
Niels Grarup: University of Copenhagen
Allan Linneberg: Bispebjerg and Frederiksberg Hospital
Young-Ae Lee: Max-Delbrück-Center for Molecular Medicine
Nicole Probst-Hensch: Swiss Tropical and Public Health Institute
Stephan Weidinger: University Hospital Schleswig-Holstein
Marjo-Riitta Jarvelin: School of Public Health,Imperial College London
Erik Melén: Karolinska Institutet
Hakon Hakonarson: Children’s Hospital of Philadelphia
Alan D. Irvine: Trinity College
Deborah Jarvis: Imperial College London
Tamar Nijsten: University Medical Center Rotterdam
Liesbeth Duijts: University Medical Center Rotterdam
Judith M. Vonk: University of Groningen, University Medical Center Groningen, GRIAC Research Institute
Gerard H. Koppelmann: University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children’s Hospital
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
Peter D. Sly: 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
Josine L. Min: University of Bristol
Sara J. Brown: University of Edinburgh
Marie Standl: Helmholtz Zentrum München - German Research Center for Environmental Health
Lavinia Paternoster: University of Bristol

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41180-2

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