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Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.
Waage, Johannes; Standl, Marie; Curtin, John A; Jessen, Leon E; Thorsen, Jonathan; Tian, Chao; Schoettler, Nathan; Flores, Carlos; Abdellaoui, Abdel; Ahluwalia, Tarunveer S; Alves, Alexessander C; Amaral, Andre F S; Antó, Josep M; Arnold, Andreas; Barreto-Luis, Amalia; Baurecht, Hansjörg; van Beijsterveldt, Catharina E M; Bleecker, Eugene R; Bonàs-Guarch, Sílvia; Boomsma, Dorret I; Brix, Susanne; Bunyavanich, Supinda; Burchard, Esteban G; Chen, Zhanghua; Curjuric, Ivan; Custovic, Adnan; den Dekker, Herman T; Dharmage, Shyamali C; Dmitrieva, Julia; Duijts, Liesbeth; Ege, Markus J; Gauderman, W James; Georges, Michel; Gieger, Christian; Gilliland, Frank; Granell, Raquel; Gui, Hongsheng; Hansen, Torben; Heinrich, Joachim; Henderson, John; Hernandez-Pacheco, Natalia; Holt, Patrick; Imboden, Medea; Jaddoe, Vincent W V; Jarvelin, Marjo-Riitta; Jarvis, Deborah L; Jensen, Kamilla K; Jónsdóttir, Ingileif; Kabesch, Michael; Kaprio, Jaakko.
Afiliação
  • Waage J; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
  • Standl M; Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Curtin JA; Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, UK.
  • Jessen LE; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
  • Thorsen J; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
  • Tian C; 23andMe, Inc., Mountain View, CA, USA.
  • Schoettler N; Department of Human Genetics, University of Chicago, Chicago, IL, USA.
  • Flores C; Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Tenerife, Spain.
  • Abdellaoui A; CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
  • Ahluwalia TS; Department of Biological Psychology, Netherlands Twin Register, VU University, Amsterdam, The Netherlands.
  • Alves AC; Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
  • Amaral AFS; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
  • Antó JM; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, UK.
  • Arnold A; Population Health and Occupational Disease, National Heart and Lung Institute, Imperial College London, London, UK.
  • Barreto-Luis A; ISGlobal, Barcelona, Spain.
  • Baurecht H; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
  • van Beijsterveldt CEM; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
  • Bleecker ER; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
  • Bonàs-Guarch S; Clinic and Polyclinic of Dermatology, University Medicine Greifswald, Greifswald, Germany.
  • Boomsma DI; Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Tenerife, Spain.
  • Brix S; Department of Dermatology, Venereology and Allergology, University-Hospital Schleswig-Hostein, Campus Kiel, Kiel, Germany.
  • Bunyavanich S; Department of Biological Psychology, Netherlands Twin Register, VU University, Amsterdam, The Netherlands.
  • Burchard EG; Divisions of Pharmacogenomics and Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, AZ, USA.
  • Chen Z; Barcelona Supercomputing Center (BSC), Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona, Spain.
  • Curjuric I; Department of Biological Psychology, Netherlands Twin Register, VU University, Amsterdam, The Netherlands.
  • Custovic A; APH Amsterdam Public Health, Amsterdam, The Netherlands.
  • den Dekker HT; Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
  • Dharmage SC; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Dmitrieva J; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Duijts L; Department of Bioengineering & Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
  • Ege MJ; Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
  • Gauderman WJ; University of Basel, Basel, Switzerland.
  • Georges M; Swiss Tropical and Public Health Institute, Basel, Switzerland.
  • Gieger C; Department of Paediatrics, Imperial College London, London, UK.
  • Gilliland F; The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Granell R; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Gui H; Department of Pediatrics, Division of Respiratory Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Hansen T; Allergy and Lung Health Unit, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
  • Heinrich J; Laboratory of Animal Genomics, Unit of Medical Genomics, GIGA Institute, University of Liège, Liège, Belgium.
  • Henderson J; The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Hernandez-Pacheco N; Department of Pediatrics, Division of Respiratory Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Holt P; Department of Pediatrics, Division of Neonatology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Imboden M; LMU Munich, Dr von Hauner Children's Hospital, Munich, and German Center for Lung Research (DZL), Munich, Germany.
  • Jaddoe VWV; Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
  • Jarvelin MR; Laboratory of Animal Genomics, Unit of Medical Genomics, GIGA Institute, University of Liège, Liège, Belgium.
  • Jarvis DL; Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Jensen KK; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Jónsdóttir I; Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
  • Kabesch M; MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Kaprio J; Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA.
Nat Genet ; 50(8): 1072-1080, 2018 08.
Article em En | MEDLINE | ID: mdl-30013184
ABSTRACT
Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Genoma Humano / Predisposição Genética para Doença / Loci Gênicos / Rinite Alérgica / Antígenos HLA Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Genoma Humano / Predisposição Genética para Doença / Loci Gênicos / Rinite Alérgica / Antígenos HLA Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article