Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12-22

AUTHORS

Florence Demenais, Patricia Margaritte-Jeannin, Kathleen C. Barnes, William O. C. Cookson, Janine Altmüller, Wei Ang, R. Graham Barr, Terri H. Beaty, Allan B. Becker, John Beilby, Hans Bisgaard, Unnur Steina Bjornsdottir, Eugene Bleecker, Klaus Bønnelykke, Dorret I. Boomsma, Emmanuelle Bouzigon, Christopher E. Brightling, Myriam Brossard, Guy G. Brusselle, Esteban Burchard, Kristin M. Burkart, Andrew Bush, Moira Chan-Yeung, Kian Fan Chung, Alexessander Couto Alves, John A. Curtin, Adnan Custovic, Denise Daley, Johan C. de Jongste, Blanca E. Del-Rio-Navarro, Kathleen M. Donohue, Liesbeth Duijts, Celeste Eng, Johan G. Eriksson, Martin Farrall, Yuliya Fedorova, Bjarke Feenstra, Manuel A. Ferreira, Maxim B. Freidin, Zofia Gajdos, Jim Gauderman, Ulrike Gehring, Frank Geller, Jon Genuneit, Sina A. Gharib, Frank Gilliland, Raquel Granell, Penelope E. Graves, Daniel F. Gudbjartsson, Tari Haahtela, Susan R. Heckbert, Dick Heederik, Joachim Heinrich, Markku Heliövaara, John Henderson, Blanca E. Himes, Hiroshi Hirose, Joel N. Hirschhorn, Albert Hofman, Patrick Holt, Jouke Hottenga, Thomas J. Hudson, Jennie Hui, Medea Imboden, Vladimir Ivanov, Vincent W. V. Jaddoe, Alan James, Christer Janson, Marjo-Riitta Jarvelin, Deborah Jarvis, Graham Jones, Ingileif Jonsdottir, Pekka Jousilahti, Michael Kabesch, Mika Kähönen, David B. Kantor, Alexandra S. Karunas, Elza Khusnutdinova, Gerard H. Koppelman, Anita L. Kozyrskyj, Eskil Kreiner, Michiaki Kubo, Rajesh Kumar, Ashish Kumar, Mikko Kuokkanen, Lies Lahousse, Tarja Laitinen, Catherine Laprise, Mark Lathrop, Susanne Lau, Young-Ae Lee, Terho Lehtimäki, Sébastien Letort, Albert M. Levin, Guo Li, Liming Liang, Laura R. Loehr, Stephanie J. London, Daan W. Loth, Ani Manichaikul, Ingo Marenholz, Fernando J. Martinez, Melanie C. Matheson, Rasika A. Mathias, Kenji Matsumoto, Hamdi Mbarek, Wendy L. McArdle, Mads Melbye, Erik Melén, Deborah Meyers, Sven Michel, Hamida Mohamdi, Arthur W. Musk, Rachel A. Myers, Maartje A. E. Nieuwenhuis, Emiko Noguchi, George T. O’Connor, Ludmila M. Ogorodova, Cameron D. Palmer, Aarno Palotie, Julie E. Park, Craig E. Pennell, Göran Pershagen, Alexey Polonikov, Dirkje S. Postma, Nicole Probst-Hensch, Valery P. Puzyrev, Benjamin A. Raby, Olli T. Raitakari, Adaikalavan Ramasamy, Stephen S. Rich, Colin F. Robertson, Isabelle Romieu, Muhammad T. Salam, Veikko Salomaa, Vivi Schlünssen, Robert Scott, Polina A. Selivanova, Torben Sigsgaard, Angela Simpson, Valérie Siroux, Lewis J. Smith, Maria Solodilova, Marie Standl, Kari Stefansson, David P. Strachan, Bruno H. Stricker, Atsushi Takahashi, Philip J. Thompson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Carla M. T. Tiesler, Dara G. Torgerson, Tatsuhiko Tsunoda, André G. Uitterlinden, Ralf J. P. van der Valk, Amaury Vaysse, Sailaja Vedantam, Andrea von Berg, Erika von Mutius, Judith M. Vonk, Johannes Waage, Nick J. Wareham, Scott T. Weiss, Wendy B. White, Magnus Wickman, Elisabeth Widén, Gonneke Willemsen, L. Keoki Williams, Inge M. Wouters, James J. Yang, Jing Hua Zhao, Miriam F. Moffatt, Carole Ober, Dan L. Nicolae

ABSTRACT

We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms. More... »

PAGES

42-53

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    1

    VOLUME

    50

    Author Affiliations

  • Institut Universitaire d’Hématologie, Université Paris Diderot, Université Sorbonne Paris Cité, Paris, France
  • Division of Biomedical Informatics and Personalized Medicine, Colorado Center for Personalized Medicine, University of Colorado, Denver, CO, USA
  • Section of Genomic Medicine, National Heart and Lung Institute, London, UK
  • Cologne Center for Genomics and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
  • School of Women’s and Infants’ Health, University of Western Australia, Perth, Western Australia, Australia
  • Departments of Medicine and Epidemiology, Columbia University, New York, NY, USA
  • Division of Genetic Epidemiology, Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
  • Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
  • Department of the Diagnostic Genomics Laboratory, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia
  • Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
  • Department of Medicine, Landspitali, National University Hospital of Iceland, Reykjavik, Iceland
  • Center for Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA
  • Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrjie Universiteit, Amsterdam, The Netherlands
  • University of Leicester, Institute for Lung Health, Glenfield Hospital, Leicester, UK
  • Department of Respiratory Medicine, Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands
  • Department of Bioengineering & Therapeutic Sciences and Medicine, University of California, San Francisco, San Francisco, CA, USA
  • Division of Pulmonary, Allergy and Critical Care, College of Physicians and Surgeons, Columbia University, New York, NY, USA
  • Royal Brompton Harefield National Health Service (NHS) Foundation Trust, London, UK
  • Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  • Biomedical Research Unit, Royal Brompton & Harefield National Health Service (NHS) Trust, London, UK
  • Department of Epidemiology and Biostatistics, Imperial College London, London, UK
  • Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
  • Department of Paediatrics, Imperial College London, London, UK
  • Centre for Heart and Lung Innovation, University of British Columbia, Vancouver, BC, Canada
  • Department of Pediatrics, Division of Respiratory Medicine, Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands
  • Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico
  • Department of Pediatrics, Division of Respiratory Medicine, and Department of Pediatrics, Division of Neonatology, Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands
  • Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
  • Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
  • Institute of Biochemistry and Genetics, Ufa Scientific Center of the Russian Academy of Sciences, Ufa, Russian Federation
  • Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
  • Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
  • Population Genetics Laboratory, Research Institute of Medical Genetics, Tomsk NRMC, Tomsk, Russian Federation
  • Broad Institute, Cambridge, MA, USA
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
  • Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
  • Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany
  • Department of Medicine, University of Washington, Seattle, WA, USA
  • MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
  • Asthma and Airway Disease Research Center and BIO5 Institute, University of Arizona, Tucson, AZ, USA
  • School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland
  • Skin and Allergy Hospital, University of Helsinki, Helsinki, Finland
  • Department of Epidemiology, University of Washington, Seattle, WA, USA
  • Institute of Epidemiology I, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany
  • National Institute for Health and Welfare (THL), Helsinki, Finland
  • Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA
  • Health Center, Department of Internal Medicine, Keio University, Tokyo, Japan
  • Departments of Pediatrics and Genetics, Harvard Medical School, Boston, MA, USA
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
  • Cell Biology Telethon Kids Institute, University of Western Australia, Subiaco, Western Australia, Australia
  • AbbVie Inc., Redwood City, CA, USA
  • School of Population and Global Health, University of Western Australia, Nedlands, Western Australia, Australia
  • University of Basel, Basel, Switzerland
  • Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, Russian Federation
  • The Generation R Study Group, Department of Pediatrics and Department of Epidemiology, Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands
  • School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia
  • Department of Medical Sciences: Respiratory, Allergy & Sleep Research, Uppsala University, Uppsala, Sweden
  • Unit of Primary Care, Oulu University Hospital, Oulu, Finland
  • MRC–PHE Centre for Environment and Health, Imperial College London, London, UK
  • School of Science and Health, Western Sydney University, Sydney, New South Wales, Australia
  • Faculty of Medicine, University of Iceland, Reykjavik, Iceland
  • Department of Pediatric Pneumology and Allergy, University Children’s Hospital Regensburg (KUNO), Regensburg, Germany
  • Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland
  • Department of Anaesthesia, Harvard Medical School, Boston, MA, USA
  • Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, Russian Federation
  • Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands
  • Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
  • RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Divison of Allergy and Clinical Immunology, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
  • Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  • Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
  • Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
  • Department of Pulmonary Medicine, University of Turku and Turku University Hospital, Turku, Finland
  • Centre de Santé et de Services Sociaux du Saguenay-Lac-Saint-Jean, Saguenay, QC, Canada
  • McGill University and Genome Quebec Innovation Centre, Montréal, QC, Canada
  • Pediatric Pneumology and Immunology, Charité Universitätsmedizin, Berlin, Germany
  • Pediatric Allergology, Experimental and Clinical Research Center, Charité Universitätsmedizin, Berlin, Germany
  • Department of Clinical Chemistry, Fimlab Laboratories, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
  • Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
  • Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
  • Division of General Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  • National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA
  • Department of Epidemiology, Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands
  • Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
  • Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia
  • Division of Allergy & Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
  • Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan
  • Bristol Bioresource Laboratories, School of Social and Community Medicine, University of Bristol, Bristol, UK
  • Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
  • Sachs Children’s Hospital, Stockholm, Sweden
  • Schools of Population Health and of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia
  • Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC, USA
  • University Medical Center Groningen, Department of Pulmonology, University of Groningen, Groningen, The Netherlands
  • Department of Medical Genetics, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
  • The National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, MA, USA
  • Department of Faculty Pediatrics, Siberian State Medical University, Tomsk, Russian Federation
  • Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital, Boston, MA, USA
  • The Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA
  • Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden
  • Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
  • Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland
  • Department of Medical and Molecular Genetics, King’s College London, London, UK
  • Respiratory Medicine, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
  • Center for Population Health Research, National Institute of Public Health, Cuernavaca, Mexico
  • Department of Psychiatry, Kern Medical, Bakersfield, CA, USA
  • Department of Public Health, Section for Environment, Occupation & Health, Aarhus University, Aarhus, Denmark
  • MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK
  • Department of Faculty Therapy, Siberian State Medical University, Tomsk, Russian Federation
  • University Hospital of South Manchester, National Health Service (NHS) Foundation Trust, Manchester, UK
  • Université de Grenoble Alpes/CNRS UMR5309, Institute for Advanced Biosciences, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Grenoble, France
  • Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
  • Population Health Research Institute, St George’s University of London, London, UK
  • Department of Internal Medicine, Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands
  • Institute for Respiratory Health and Harry Perkins Institute of Medical Research, University of Western Australia and The Lung Health Clinic, Nedlands, Western Australia, Australia
  • deCODE genetics, Amgen Inc., Reykjavik, Iceland
  • Division of Metabolic Diseases and Nutritional Medicine, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany
  • Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
  • The Generation R Study Group, Department of Pediatrics, Division of Respiratory Medicine and Department of Epidemiology, Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands
  • Department of Pediatrics, Marien-Hospital Wesel, Wesel, Germany
  • German Center for Lung Research, Munich, Germany
  • University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands
  • Undergraduate Training and Education Center (UTEC), Jackson Heart Study, Tougaloo College, Jackson, MI, USA
  • Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden
  • Department of Internal Medicine, Henry Ford Health System, Detroit, MI, USA
  • School of Nursing, University of Michigan, Ann Arbor, MI, USA
  • Department of Human Genetics, University of Chicago, Chicago, IL, USA
  • Departments of Statistics, Human Genetics and Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-017-0014-7

    DOI

    http://dx.doi.org/10.1038/s41588-017-0014-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1099864983

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29273806


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