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Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis

Ishigaki K 1 , Sakaue S 1 , Terao C 2 , Luo Y 1 , Sonehara K 3 , Yamaguchi K 4 Show all authors , Amariuta T 1 , Too CL 5 , Laufer VA 6 , Scott IC 7 , Viatte S 8 , Takahashi M 9 , Ohmura K 10 , Murasawa A 11 , Hashimoto M 12 , Ito H 12 , Hammoudeh M 13 , Emadi SA 13 , Masri BK 14 , Halabi H 15 , Badsha H 16 , Uthman IW 17 , Wu X 18 , Lin L 18 , Li T 18 , Plant D 8 , Barton A 8 , Orozco G 8 , Verstappen SMM 19 , Bowes J 8 , MacGregor AJ 20 , Honda S 21 , Koido M 2 , Tomizuka K 2 , Kamatani Y 2 , Tanaka H 22 , Tanaka E 21 , Suzuki A 23 , Maeda Y 24 , Yamamoto K 3 , Miyawaki S 25 , Xie G 26 , Zhang J 26 , Amos CI 27 , Keystone E 28 , Wolbink G 29 , van der Horst-Bruinsma I 30 , Cui J 31 , Liao KP 31 , Carroll RJ 32 , Lee HS 33 , Bang SY 33 , Siminovitch KA 26 , de Vries N 34 , Alfredsson L 35 , Rantapää-Dahlqvist S 36 , Karlson EW 31 , Bae SC 33 , Kimberly RP 37 , Edberg JC 37 , Mariette X 38 , Huizinga T 39 , Dieudé P 40 , Schneider M 41 , Kerick M 42 , Denny JC 32 , BioBank Japan Project , Matsuda K 43 , Matsuo K 44 , Mimori T 10 , Matsuda F 9 , Fujio K 45 , Tanaka Y 22 , Kumanogoh A 24 , Traylor M 46 , Lewis CM 46 , Eyre S 8 , Xu H 18 , Saxena R 47 , Arayssi T 48 , Kochi Y 4 , Ikari K 21 , Harigai M 21 , Gregersen PK 49 , Yamamoto K 23 , Louis Bridges S 50 , Padyukov L 51 , Martin J 42 , Klareskog L 51 , Okada Y 52 , Raychaudhuri S 53

Affiliations 

  • 1 Center for Data Sciences, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
  • 2 Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • 3 Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan
  • 4 Department of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
  • 5 Immunogenetics Unit, Allergy and Immunology Research Center, Institute for Medical Research, National Institutes of Health Complex, Ministry of Health, Kuala Lumpur, Malaysia
  • 6 Department of Clinical Immunology and Rheumatology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA
  • 7 Haywood Academic Rheumatology Centre, Haywood Hospital, Midlands Partnership NHS Foundation Trust, Burslem, UK
  • 8 Centre for Genetics and Genomics Versus Arthritis, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
  • 9 Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • 10 Department of Rheumatology and Clinical immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • 11 Department of Rheumatology, Niigata Rheumatic Center, Niigata, Japan
  • 12 Department of Advanced Medicine for Rheumatic Diseases, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • 13 Rheumatology Division, Department of Internal Medicine, Hamad Medical Corporation, Doha, Qatar
  • 14 Department of Internal Medicine, Jordan Hospital, Amman, Jordan
  • 15 Section of Rheumatology, Department of Internal Medicine, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
  • 16 Dr. Humeira Badsha Medical Center, Emirates Hospital, Dubai, United Arab Emirates
  • 17 Department of Rheumatology, American University of Beirut, Beirut, Lebanon
  • 18 Department of Rheumatology and Immunology, Shanghai Changzeng Hospital, The Second Military Medical University, Shanghai, China
  • 19 NIHR Manchester Biomedical Research Centre, Manchester University Foundation Trust, Manchester, UK
  • 20 Norwich Medical School, University of East Anglia, Norwich, UK
  • 21 Institute of Rheumatology, Tokyo Women's Medical University Hospital, Tokyo, Japan
  • 22 The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health Japan, Kitakyushu, Japan
  • 23 Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • 24 Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan
  • 25 Department of Neurosurgery, Faculty of Medicine, the University of Tokyo, Tokyo, Japan
  • 26 Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada
  • 27 Baylor College of Medicine, Houston, TX, USA
  • 28 The University of Toronto, Toronto, Ontario, Canada
  • 29 Department of Rheumatology, Amsterdam Rheumatology and Immunology Center (ARC), Reade, Amsterdam, the Netherlands
  • 30 Department of Rheumatology & Clinical Immunology/ARC, Amsterdam Institute for Infection and Immunity, Amsterdam UMC location Vrije Universiteit, Amsterdam, the Netherlands
  • 31 Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
  • 32 Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, USA
  • 33 Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
  • 34 Department of Rheumatology & Clinical Immunology/ARC, Amsterdam Institute for Infection and Immunity, Amsterdam UMC location AMC/University of Amsterdam, Amsterdam, the Netherlands
  • 35 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  • 36 Department of Public Health and Clinical Medicine, Rheumatology, Umeå University, Umeå, Sweden
  • 37 Center for Clinical and Translational Science, Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
  • 38 Department of Rheumatology, Université Paris-Saclay, Assistance Pubique - Hôpitaux de Paris, Hôpital Bicêtre, INSERM UMR1184, Le Kremlin Bicêtre, France
  • 39 Leiden University Medical Center, Leiden, the Netherlands
  • 40 University of Paris Cité, Inserm, PHERE, F-75018, Paris, France
  • 41 Department of Rheumatology & Hiller Research Unit Rheumatology, UKD, Heinrich-Heine University, Düsseldorf, Germany
  • 42 Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain
  • 43 Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • 44 Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan
  • 45 Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  • 46 Department of Medical & Molecular Genetics, King's College London, London, UK
  • 47 Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • 48 Department of Internal Medicine, Weill Cornell Medicine-Qatar, Education City, Doha, Qatar
  • 49 Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA
  • 50 Department of Medicine, Hospital for Special Surgery, New York, NY, USA
  • 51 Department of Medicine, Division of Rheumatology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
  • 52 Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan. yokada@sg.med.osaka-u.ac.jp
  • 53 Center for Data Sciences, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org
Nat Genet, 2022 Nov;54(11):1640-1651.
PMID: 36333501 DOI: 10.1038/s41588-022-01213-w

Abstract

Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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