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

Affiliations

• ¹ Genetic Variation and Human Diseases Unit (UMR-946), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France. florence.demenais@inserm.fr.
• ² Institut Universitaire d'Hématologie, Université Paris Diderot, Université Sorbonne Paris Cité, Paris, France. florence.demenais@inserm.fr.
• ³ Genetic Variation and Human Diseases Unit (UMR-946), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
• ⁴ Institut Universitaire d'Hématologie, Université Paris Diderot, Université Sorbonne Paris Cité, Paris, France.
• ⁵ Division of Biomedical Informatics and Personalized Medicine, Colorado Center for Personalized Medicine, University of Colorado, Denver, CO, USA.
• ⁶ Section of Genomic Medicine, National Heart and Lung Institute, London, UK.
• ⁷ Cologne Center for Genomics and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
• ⁸ School of Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia.
• ⁹ Departments of Medicine and Epidemiology, Columbia University, New York, NY, USA.
• ¹⁰ Division of Genetic Epidemiology, Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
• ¹¹ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada.
• ¹² Department of the Diagnostic Genomics Laboratory, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia.
• ¹³ Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
• ¹⁴ Department of Medicine, Landspitali, National University Hospital of Iceland, Reykjavik, Iceland.
• ¹⁵ Center for Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
• ¹⁶ Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrjie Universiteit, Amsterdam, The Netherlands.
• ¹⁷ University of Leicester, Institute for Lung Health, Glenfield Hospital, Leicester, UK.
• ¹⁸ Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
• ¹⁹ Department of Epidemiology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
• ²⁰ Department of Respiratory Medicine, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
• ²¹ Department of Bioengineering & Therapeutic Sciences and Medicine, University of California, San Francisco, San Francisco, CA, USA.
• ²² Division of Pulmonary, Allergy and Critical Care, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
• ²³ National Heart and Lung Institute, Imperial College London, London, UK.
• ²⁴ Royal Brompton Harefield National Health Service (NHS) Foundation Trust, London, UK.
• ²⁵ Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
• ²⁶ Biomedical Research Unit, Royal Brompton & Harefield National Health Service (NHS) Trust, London, UK.
• ²⁷ Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
• ²⁸ 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.
• ²⁹ Department of Paediatrics, Imperial College London, London, UK.
• ³⁰ Centre for Heart and Lung Innovation, University of British Columbia, Vancouver, BC, Canada.
• ³¹ Department of Pediatrics, Division of Respiratory Medicine, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
• ³² Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico.
• ³³ Department of Pediatrics, Division of Respiratory Medicine, and Department of Pediatrics, Division of Neonatology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
• ³⁴ Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
• ³⁵ Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
• ³⁶ Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
• ³⁷ Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
• ³⁸ Institute of Biochemistry and Genetics, Ufa Scientific Center of the Russian Academy of Sciences, Ufa, Russian Federation.
• ³⁹ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
• ⁴⁰ Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
• ⁴¹ Population Genetics Laboratory, Research Institute of Medical Genetics, Tomsk NRMC, Tomsk, Russian Federation.
• ⁴² Divisions of Genetics and Endocrinology, Children's Hospital, Boston, MA, USA.
• ⁴³ Broad Institute, Cambridge, MA, USA.
• ⁴⁴ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
• ⁴⁵ Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
• ⁴⁶ Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
• ⁴⁷ Department of Medicine, University of Washington, Seattle, WA, USA.
• ⁴⁸ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
• ⁴⁹ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
• ⁵⁰ Asthma and Airway Disease Research Center and BIO5 Institute, University of Arizona, Tucson, AZ, USA.
• ⁵¹ deCODE genetics, Amgen Inc., Reykjavik, Iceland.
• ⁵² School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
• ⁵³ Skin and Allergy Hospital, University of Helsinki, Helsinki, Finland.
• ⁵⁴ Department of Epidemiology, University of Washington, Seattle, WA, USA.
• ⁵⁵ Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital in Munich, Munich, Germany.
• ⁵⁶ Institute of Epidemiology I, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany.
• ⁵⁷ National Institute for Health and Welfare (THL), Helsinki, Finland.
• ⁵⁸ Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA.
• ⁵⁹ Health Center, Department of Internal Medicine, Keio University, Tokyo, Japan.
• ⁶⁰ Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA, USA.
• ⁶¹ Departments of Pediatrics and Genetics, Harvard Medical School, Boston, MA, USA.
• ⁶² Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
• ⁶³ Cell Biology Telethon Kids Institute, University of Western Australia, Subiaco, Western Australia, Australia.
• ⁶⁴ Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
• ⁶⁵ AbbVie Inc., Redwood City, CA, USA.
• ⁶⁶ Busselton Population Medical Research Institute, Perth, Western Australia, Australia.
• ⁶⁷ School of Population and Global Health, University of Western Australia, Nedlands, Western Australia, Australia.
• ⁶⁸ Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.
• ⁶⁹ University of Basel, Basel, Switzerland.
• ⁷⁰ Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, Russian Federation.
• ⁷¹ The Generation R Study Group, Department of Pediatrics and Department of Epidemiology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
• ⁷² Department of Pulmonary Physiology and Sleep Medicine, Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
• ⁷³ School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.
• ⁷⁴ Department of Medical Sciences: Respiratory, Allergy & Sleep Research, Uppsala University, Uppsala, Sweden.
• ⁷⁵ Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, UK.
• ⁷⁶ Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
• ⁷⁷ Biocenter Oulu, University of Oulu, Oulu, Finland.
• ⁷⁸ Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
• ⁷⁹ MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.
• ⁸⁰ School of Science and Health, Western Sydney University, Sydney, New South Wales, Australia.
• ⁸¹ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
• ⁸² Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany.
• ⁸³ Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland.
• ⁸⁴ Department of Anesthesiology, Perioperative and Pain Medicine, Division of Critical Care Medicine, Boston Children's Hospital, Boston, MA, USA.
• ⁸⁵ Department of Anaesthesia, Harvard Medical School, Boston, MA, USA.
• ⁸⁶ Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, Russian Federation.
• ⁸⁷ University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, Groningen, The Netherlands.
• ⁸⁸ Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.
• ⁸⁹ Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
• ⁹⁰ RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
• ⁹¹ Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
• ⁹² Divison of Allergy and Clinical Immunology, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
• ⁹³ Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
• ⁹⁴ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
• ⁹⁵ Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
• ⁹⁶ Department of Pulmonary Medicine, University of Turku and Turku University Hospital, Turku, Finland.
• ⁹⁷ Département des Sciences Fondamentales, Université du Québec à Chicoutimi, Chicoutimi, Quebec, Canada.
• ⁹⁸ Centre de Santé et de Services Sociaux du Saguenay-Lac-Saint-Jean, Saguenay, QC, Canada.
• ⁹⁹ McGill University and Genome Quebec Innovation Centre, Montréal, QC, Canada.
• ¹⁰⁰ Pediatric Pneumology and Immunology, Charité Universitätsmedizin, Berlin, Germany.
• ¹⁰¹ Max-Delbrück-Centrum (MDC) for Molecular Medicine, Berlin, Germany.
• ¹⁰² Pediatric Allergology, Experimental and Clinical Research Center, Charité Universitätsmedizin, Berlin, Germany.
• ¹⁰³ Department of Clinical Chemistry, Fimlab Laboratories, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
• ¹⁰⁴ Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA.
• ¹⁰⁵ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
• ¹⁰⁶ Division of General Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
• ¹⁰⁷ National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA.
• ¹⁰⁸ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
• ¹⁰⁹ Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
• ¹¹⁰ Division of Allergy & Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
• ¹¹¹ Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
• ¹¹² Bristol Bioresource Laboratories, School of Social and Community Medicine, University of Bristol, Bristol, UK.
• ¹¹³ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
• ¹¹⁴ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
• ¹¹⁵ Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden.
• ¹¹⁶ Sachs Children's Hospital, Stockholm, Sweden.
• ¹¹⁷ Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
• ¹¹⁸ Schools of Population Health and of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
• ¹¹⁹ Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC, USA.
• ¹²⁰ University Medical Center Groningen, Department of Pulmonology, University of Groningen, Groningen, The Netherlands.
• ¹²¹ Department of Medical Genetics, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
• ¹²² Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
• ¹²³ The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA.
• ¹²⁴ Department of Faculty Pediatrics, Siberian State Medical University, Tomsk, Russian Federation.
• ¹²⁵ Analytic and Translational Genetics Unit, Departments of Medicine, of Neurology and of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
• ¹²⁶ The Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
• ¹²⁷ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
• ¹²⁸ Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland.
• ¹²⁹ Department of Medical and Molecular Genetics, King's College London, London, UK.
• ¹³⁰ Respiratory Medicine, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
• ¹³¹ Hubert Department of Global Health, Mory University, Atlanta, GA, USA.
• ¹³² Center for Population Health Research, National Institute of Public Health, Cuernavaca, Mexico.
• ¹³³ Department of Psychiatry, Kern Medical, Bakersfield, CA, USA.
• ¹³⁴ Department of Public Health, Section for Environment, Occupation & Health, Aarhus University, Aarhus, Denmark.
• ¹³⁵ MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
• ¹³⁶ Department of Faculty Therapy, Siberian State Medical University, Tomsk, Russian Federation.
• ¹³⁷ University Hospital of South Manchester, National Health Service (NHS) Foundation Trust, Manchester, UK.
• ¹³⁸ Institut National de la Santé et de la Recherche Médicale (INSERM) U1209, Institute for Advanced Biosciences, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Grenoble, France.
• ¹³⁹ Université de Grenoble Alpes/CNRS UMR5309, Institute for Advanced Biosciences, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Grenoble, France.
• ¹⁴⁰ Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
• ¹⁴¹ Population Health Research Institute, St George's University of London, London, UK.
• ¹⁴² Netherlands Healthcare Inspectorate, The Hague, The Netherlands.
• ¹⁴³ Department of Internal Medicine, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
• ¹⁴⁴ Institute for Respiratory Health and Harry Perkins Institute of Medical Research, University of Western Australia and The Lung Health Clinic, Nedlands, Western Australia, Australia.
• ¹⁴⁵ Division of Metabolic Diseases and Nutritional Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany.
• ¹⁴⁶ Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
• ¹⁴⁷ 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.
• ¹⁴⁸ Department of Pediatrics, Marien-Hospital Wesel, Wesel, Germany.
• ¹⁴⁹ Dr. Von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany.
• ¹⁵⁰ German Center for Lung Research, Munich, Germany.
• ¹⁵¹ University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.
• ¹⁵² Undergraduate Training and Education Center (UTEC), Jackson Heart Study, Tougaloo College, Jackson, MI, USA.
• ¹⁵³ Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden.
• ¹⁵⁴ Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA.
• ¹⁵⁵ Department of Internal Medicine, Henry Ford Health System, Detroit, MI, USA.
• ¹⁵⁶ School of Nursing, University of Michigan, Ann Arbor, MI, USA.
• ¹⁵⁷ Department of Human Genetics, University of Chicago, Chicago, IL, USA.
• ¹⁵⁸ Departments of Statistics, Human Genetics and Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL, USA. nicolae@galton.uchicago.edu.