Nature Communications (Oct 2023)
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,
- 23andMe Research Team,
- Suyash S. Shringarpure,
- Ruth Mitchell,
- Kadri Reis,
- Anu Reigo,
- Estonian Biobank Research Team,
- 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,
- Lavinia Paternoster
Affiliations
- Ashley Budu-Aggrey
- Medical Research Council Integrative Epidemiology Unit, Bristol Medical School, University of Bristol
- Anna Kilanowski
- Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
- Maria K. Sobczyk
- Medical Research Council Integrative Epidemiology Unit, Bristol Medical School, University of Bristol
- 23andMe Research Team
- Suyash S. Shringarpure
- 23andMe, Inc.
- Ruth Mitchell
- Medical Research Council Integrative Epidemiology Unit, Bristol Medical School, University of Bristol
- Kadri Reis
- Estonian Genome Centre, Institute of Genomics, University of Tartu
- Anu Reigo
- Estonian Genome Centre, Institute of Genomics, University of Tartu
- Estonian Biobank Research Team
- Reedik Mägi
- Estonian Genome Centre, Institute of Genomics, University of Tartu
- Mari Nelis
- Estonian Genome Centre, Institute of Genomics, University of Tartu
- Nao Tanaka
- Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences
- Ben M. Brumpton
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology
- Laurent F. Thomas
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology
- Pol Sole-Navais
- Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg
- Christopher Flatley
- Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg
- Antonio Espuela-Ortiz
- Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna
- Esther Herrera-Luis
- Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna
- Jesus V. T. Lominchar
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen
- Jette Bork-Jensen
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, 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
- Department of Health Sciences, University of Leicester
- Hansjorg Baurecht
- Department of Epidemiology and Preventive Medicine, University of Regensburg
- Elke Rodriguez
- Department of Dermatology and Allergy, University Hospital Schleswig-Holstein
- Alexessander Couto Alves
- School of Biosciences and Medicine, University of Surrey
- Ashish Kumar
- Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet
- Patrick M. Sleiman
- Center for Applied Genomics, Children’s Hospital of Philadelphia
- Xiao Chang
- Center for Applied Genomics, Children’s Hospital of Philadelphia
- Carolina Medina-Gomez
- The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam
- Chen Hu
- The Generation R Study Group, Erasmus MC, 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
- MRC Lifecourse Epidemiology Centre, University of Southampton
- Philip Titcombe
- MRC Lifecourse Epidemiology Centre, University of Southampton
- Elie Antoun
- Faculty of Medicine, University of Southampton
- João Fadista
- Department of Bioinformatics & Data Mining
- Carol A. Wang
- School of Medicine and Public Health, University of Newcastle
- Elisabeth Thiering
- Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
- Baojun Wu
- Center for Individualized and Genomic Medicine Research (CIGMA), Department of Medicine, Henry Ford Health
- Sara Kress
- Environmental Epidemiology of Lung, Brain and Skin Aging, IUF – Leibniz Research Institute for Environmental Medicine
- Dilini M. Kothalawala
- Human Development and Health, Faculty of Medicine, University of Southampton
- Latha Kadalayil
- Human Development and Health, Faculty of Medicine, University of Southampton
- Jiasong Duan
- Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis
- Hongmei Zhang
- Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis
- Sabelo Hadebe
- Division of Immunology, Department of Pathology, Faculty of Health Sciences, University of Cape Town
- Thomas Hoffmann
- Institute for Human Genetics, UCSF
- Eric Jorgenson
- Regeneron Genetics Center
- Hélène Choquet
- Division of Research, Kaiser Permanente Northern California
- Neil Risch
- Institute for Human Genetics, UCSF
- Pål Njølstad
- Center for Diabetes Research, Department of Clinical Science, University of Bergen
- Ole A. Andreassen
- NORMENT Centre, Institute of Clinical Medicine, University of Oslo
- Stefan Johansson
- Center for Diabetes Research, Department of Clinical Science, University of Bergen
- Catarina Almqvist
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Tong Gong
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Vilhelmina Ullemar
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Robert Karlsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Patrik K. E. Magnusson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Agnieszka Szwajda
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Esteban G. Burchard
- Department of Medicine, University of California San Francisco
- Jacob P. Thyssen
- Department of Dermatology, Bispebjerg Hospital, University of Copenhagen
- Torben Hansen
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen
- Line L. Kårhus
- Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital
- Thomas M. Dantoft
- Center for Clinical Research and Prevention, 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
- Clinic and Polyclinic of Dermatology, University Medicine Greifswald
- Georg Homuth
- Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald
- Susanne Lau
- Department of Pediatric Respiratory Medicine, Immunology, and Critical Care Medicine, Charité-Universitätsmedizin Berlin
- Markus M. Nöthen
- Institute of Human Genetics, 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
- Department of Twin Research & Genetics Epidemiology, Kings College London
- Mario Falchi
- Department of Twin Research & Genetics Epidemiology, Kings College London
- Veronique Bataille
- Department of Twin Research & Genetics Epidemiology, Kings College London
- Pirro Hysi
- Department of Twin Research & Genetics Epidemiology, Kings College London
- Natalia Ballardini
- Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet
- Dorret I. Boomsma
- Dept Biological Psychology, Netherlands Twin Register, VU University
- Jouke J. Hottenga
- Dept Biological Psychology, Netherlands Twin Register, VU University
- Martina Müller-Nurasyid
- Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
- Tarunveer S. Ahluwalia
- COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen
- Jakob Stokholm
- COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen
- Bo Chawes
- COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen
- Ann-Marie M. Schoos
- COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen
- Ana Esplugues
- Nursing School, University of Valencia, FISABIO-University Jaume I-University of Valencia
- Mariona Bustamante
- ISGlobal, Institute for Global Health
- Benjamin Raby
- Channing Division of Network Medicine, Brigham & Women’s Hospital and Harvard Medical School
- Syed Arshad
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton
- Chris German
- 23andMe, Inc.
- Tõnu Esko
- Estonian Genome Centre, Institute of Genomics, University of Tartu
- Lili A. Milani
- Estonian Genome Centre, Institute of Genomics, University of Tartu
- Andres Metspalu
- Estonian Genome Centre, Institute of Genomics, University of Tartu
- Chikashi Terao
- Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences
- Katrina Abuabara
- Department 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
- Kristian Hveem
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology
- Bo Jacobsson
- Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg
- Maria Pino-Yanes
- Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna
- David P. Strachan
- Population Health Research Institute, St George’s, University of London, Cranmer Terrace
- Niels Grarup
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen
- Allan Linneberg
- Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital
- Young-Ae Lee
- Max-Delbrück-Center for Molecular Medicine
- Nicole Probst-Hensch
- Swiss Tropical and Public Health Institute
- Stephan Weidinger
- Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein
- Marjo-Riitta Jarvelin
- Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health,Imperial College London
- Erik Melén
- Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet
- Hakon Hakonarson
- Center for Applied Genomics, Children’s Hospital of Philadelphia
- Alan D. Irvine
- Department of Clinical Medicine, Trinity College
- Deborah Jarvis
- Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London
- Tamar Nijsten
- Department of Dermatology, Erasmus MC, University Medical Center Rotterdam
- Liesbeth Duijts
- Department of Pediatrics, division of Respiratory Medicine and Allergology, Erasmus MC, 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
- MRC Lifecourse Epidemiology Centre and NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust
- Sheila J. Barton
- MRC Lifecourse Epidemiology Centre, University of Southampton
- Bjarke Feenstra
- Department of Epidemiology Research, Statens Serum Institut
- Craig E. Pennell
- School of Medicine and Public Health, University of Newcastle
- Peter D. Sly
- Children’s Health and Environment Program, Child Health Research Centre, The University of Queensland
- Patrick G. Holt
- Telethon Kids Institute, University of Western Australia
- L. Keoki Williams
- Center for Individualized and Genomic Medicine Research (CIGMA), Department of Medicine, Henry Ford Health
- Hans Bisgaard
- COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen
- Klaus Bønnelykke
- COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen
- John Curtin
- Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, and Manchester University NHS Foundation Trust
- Angela Simpson
- Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, and Manchester University NHS Foundation Trust
- Clare Murray
- Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, and Manchester University NHS Foundation Trust
- Tamara Schikowski
- Environmental Epidemiology of Lung, Brain and Skin Aging, Leibniz Research Institute for Environmental Medicine
- Supinda Bunyavanich
- Division of Allergy and Immunology, Department of Pediatrics, and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai
- Scott T. Weiss
- Channing Division of Network Medicine, Brigham & Women’s Hospital and Harvard Medical School
- John W. Holloway
- Human Development and Health, Faculty of Medicine, University of Southampton
- Josine L. Min
- Medical Research Council Integrative Epidemiology Unit, Bristol Medical School, University of Bristol
- Sara J. Brown
- Centre for Genomics and Experimental Medicine, Institute for Genetics and Cancer, University of Edinburgh
- Marie Standl
- Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
- Lavinia Paternoster
- Medical Research Council Integrative Epidemiology Unit, Bristol Medical School, University of Bristol
- DOI
- https://doi.org/10.1038/s41467-023-41180-2
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 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.
