TYK2 Protein-Coding Variants Protect against Rheumatoid Arthritis and Autoimmunity, with No Evidence of Major Pleiotropic Effects on Non-Autoimmune Complex Traits

• Dorothée Diogo ,

  * E-mail: dorothee.diogo@merck.com

  Current address: Merck Research Laboratories, Boston, Massachusetts, United States of America

  Affiliations Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Partners HealthCare Center for Personalized Genetic Medicine, Boston, Massachusetts, United States of America

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• Lisa Bastarache,

  Affiliation Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee, United States of America

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• Katherine P. Liao,

  Affiliation Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America

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• Robert R. Graham,

  Affiliation ITGR Human Genetics Group, Genentech Inc, San Francisco, California, United States of America

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• Robert S. Fulton,

  Affiliation The Genome Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America

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• Jeffrey D. Greenberg,

  Affiliation New York University Hospital for Joint Diseases, New York, New York, United States of America

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• Steve Eyre,

  Affiliation Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom

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• John Bowes,

  Affiliation Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom

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• Jing Cui,

  Affiliation Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America

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• Annette Lee,

  Affiliation The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York, United States of America

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• Dimitrios A. Pappas,

  Affiliation Columbia University, College of Physicians and Surgeons, New York, New York, United States of America

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• Joel M. Kremer,

  Affiliation The Albany Medical College and The Center for Rheumatology, Albany, New York, United States of America

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• Anne Barton,

  Affiliation Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom

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• Marieke J. H. Coenen,

  Affiliation Radboud university medical center, Radboud Institute for Health Sciences, Department of Human Genetics, Nijmegen, The Netherlands

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• Barbara Franke,

  Affiliation Radboud University Medical Center, Donders Centre for Neurosciences, Department of Psychiatry and Human Genetics, Nijmegen, The Netherlands

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• Lambertus A. Kiemeney,

  Affiliation Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands

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• Xavier Mariette,

  Affiliations Université Paris-Sud, Orsay, France, APHP–Hôpital Bicêtre, INSERM U1012, Le Kremlin Bicêtre, Paris, France

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• Corrine Richard-Miceli,

  Affiliations Université Paris-Sud, Orsay, France, APHP–Hôpital Bicêtre, INSERM U1012, Le Kremlin Bicêtre, Paris, France

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• Helena Canhão,

  Affiliations Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal, Rheumatology Department, Santa Maria Hospital–CHLN, Lisbon, Portugal

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• João E. Fonseca,

  Affiliations Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal, Rheumatology Department, Santa Maria Hospital–CHLN, Lisbon, Portugal

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• Niek de Vries,

  Affiliation Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology & Rheumatology, Academic Medical Center /University of Amsterdam, Amsterdam, The Netherlands

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• Paul P. Tak,

  Current address: University of Cambridge, Cambridge, United Kingdom, and GlaxoSmithkline, Stevenage, United Kingdom

  Affiliation Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology & Rheumatology, Academic Medical Center /University of Amsterdam, Amsterdam, The Netherlands

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• J. Bart A. Crusius,

  Affiliation Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands

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• Michael T. Nurmohamed,

  Affiliation Amsterdam Rheumatology and Immunology Center, Department of Rheumatology, Reade, Amsterdam, The Netherlands

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• Fina Kurreeman,

  Affiliation Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands

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• Ted R. Mikuls,

  Affiliation Division of Rheumatology and Immunology, Omaha VA and University of Nebraska Medical Center, Omaha, Nebraska, United States of America

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• Yukinori Okada,

  Current address: Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, and Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

  Affiliations Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America

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• Eli A. Stahl,

  Current address: Division of Psychiatric Genomics, Mt. Sinai School of Medicine, New York, New York, United States of America

  Affiliations Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America

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• David E. Larson,

  Affiliation The Genome Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America

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• Tracie L. Deluca,

  Affiliation The Genome Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America

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• Michelle O'Laughlin,

  Affiliation The Genome Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America

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• Catrina C. Fronick,

  Affiliation The Genome Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America

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• Lucinda L. Fulton,

  Affiliation The Genome Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America

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• Roman Kosoy,

  Affiliation Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, California, United States of America

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• Michael Ransom,

  Affiliation Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, California, United States of America

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• Tushar R. Bhangale,

  Affiliation ITGR Human Genetics Group, Genentech Inc, San Francisco, California, United States of America

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• Ward Ortmann,

  Affiliation ITGR Human Genetics Group, Genentech Inc, San Francisco, California, United States of America

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• Andrew Cagan,

  Affiliation Information Systems, Partners Healthcare, Charlestown, Massachusetts, United States of America

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• Vivian Gainer,

  Affiliation Information Systems, Partners Healthcare, Charlestown, Massachusetts, United States of America

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• Elizabeth W. Karlson,

  Affiliation Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America

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• Isaac Kohane,

  Affiliation Information Systems, Partners Healthcare, Charlestown, Massachusetts, United States of America

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• Shawn N. Murphy,

  Affiliation Information Systems, Partners Healthcare, Charlestown, Massachusetts, United States of America

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• Javier Martin,

  Affiliation Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Granada, 18100, Spain

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• Alexandra Zhernakova,

  Affiliations Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands, Genetics Department, University Medical Center and Groningen University, Groningen, The Netherlands

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• Lars Klareskog,

  Affiliation Rheumatology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden

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• Leonid Padyukov,

  Affiliation Rheumatology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden

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• Jane Worthington,

  Affiliation Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom

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• Elaine R. Mardis,

  Affiliation The Genome Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America

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• Michael F. Seldin,

  Affiliation Division of Rheumatology and Immunology, Omaha VA and University of Nebraska Medical Center, Omaha, Nebraska, United States of America

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• Peter K. Gregersen,

  Affiliation The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York, United States of America

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• Timothy Behrens,

  Affiliation ITGR Human Genetics Group, Genentech Inc, San Francisco, California, United States of America

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• Soumya Raychaudhuri,

  Affiliations Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Partners HealthCare Center for Personalized Genetic Medicine, Boston, Massachusetts, United States of America, Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom

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• Joshua C. Denny,

  Affiliations Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee, United States of America, Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America

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•  [ ... ],
• Robert M. Plenge

  Current address: Merck Research Laboratories, Boston, Massachusetts, United States of America

  Affiliations Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America

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