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European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.
Budu-Aggrey, Ashley; Kilanowski, Anna; Sobczyk, Maria K; Shringarpure, Suyash S; Mitchell, Ruth; Reis, Kadri; Reigo, Anu; Mägi, Reedik; Nelis, Mari; Tanaka, Nao; Brumpton, Ben M; Thomas, Laurent F; Sole-Navais, Pol; Flatley, Christopher; Espuela-Ortiz, Antonio; Herrera-Luis, Esther; Lominchar, Jesus V T; Bork-Jensen, Jette; Marenholz, Ingo; Arnau-Soler, Aleix; Jeong, Ayoung; Fawcett, Katherine A; Baurecht, Hansjorg; Rodriguez, Elke; Alves, Alexessander Couto; Kumar, Ashish; Sleiman, Patrick M; Chang, Xiao; Medina-Gomez, Carolina; Hu, Chen; Xu, Cheng-Jian; Qi, Cancan; El-Heis, Sarah; Titcombe, Philip; Antoun, Elie; Fadista, João; Wang, Carol A; Thiering, Elisabeth; Wu, Baojun; Kress, Sara; Kothalawala, Dilini M; Kadalayil, Latha; Duan, Jiasong; Zhang, Hongmei; Hadebe, Sabelo; Hoffmann, Thomas; Jorgenson, Eric; Choquet, Hélène; Risch, Neil; Njølstad, Pål.
Afiliação
  • Budu-Aggrey A; Medical Research Council Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, England.
  • Kilanowski A; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England.
  • Sobczyk MK; Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
  • Shringarpure SS; Pettenkofer School of Public Health, Ludwig-Maximilians University Munich, Munich, Germany.
  • Mitchell R; Medical Research Council Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, England.
  • Reis K; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England.
  • Mägi R; Medical Research Council Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, England.
  • Nelis M; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England.
  • Tanaka N; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Brumpton BM; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Sole-Navais P; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Flatley C; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Espuela-Ortiz A; Core Facility of Genomics, University of Tartu, Tartu, Estonia.
  • Herrera-Luis E; Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Lominchar JVT; Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
  • Bork-Jensen J; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, 7030, Norway.
  • Marenholz I; HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, 7600, Norway.
  • Arnau-Soler A; Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, 7030, Norway.
  • Jeong A; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, 7030, Norway.
  • Fawcett KA; Department of Clinical and Molecular Medicine, NTNU Norwegian University of Science and Technology, Trondheim, Norway.
  • Baurecht H; BioCore - Bioinformatics Core Facility, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  • Rodriguez E; Clinic of Laboratory Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
  • Alves AC; Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Kumar A; Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Sleiman PM; Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, La Laguna, Tenerife, Spain.
  • Chang X; Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, La Laguna, Tenerife, Spain.
  • Medina-Gomez C; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, København, Denmark.
  • Hu C; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, København, Denmark.
  • Xu CJ; Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
  • Qi C; Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • El-Heis S; Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
  • Titcombe P; Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • Antoun E; Swiss Tropical and Public Health Institute, CH-4123, Basel, Switzerland.
  • Fadista J; University of Basel, CH-4001, Basel, Switzerland.
  • Wang CA; Department of Health Sciences, University of Leicester, Leicester, LE1 7RH, UK.
  • Thiering E; Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.
  • Wu B; Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany.
  • Kress S; School of Biosciences and Medicine, University of Surrey, Guildford, UK.
  • Kothalawala DM; Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Solna, Sweden.
  • Kadalayil L; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
  • Duan J; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
  • Zhang H; Rhythm Pharmaceuticals, 222 Berkley Street, Boston, 02116, USA.
  • Hadebe S; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
  • Hoffmann T; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Jorgenson E; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Choquet H; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Risch N; Department of Dermatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Njølstad P; University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children's Hospital, Groningen, The Netherlands.
Nat Commun ; 14(1): 6172, 2023 10 04.
Article em En | MEDLINE | ID: mdl-37794016
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dermatite Atópica / Estudo de Associação Genômica Ampla Idioma: En Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dermatite Atópica / Estudo de Associação Genômica Ampla Idioma: En Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Reino Unido