Genetics of rheumatoid arthritis contributes to biology and drug discovery

Yukinori Okada (), Di Wu, Gosia Trynka, Towfique Raj, Chikashi Terao, Katsunori Ikari, Yuta Kochi, Koichiro Ohmura, Akari Suzuki, Shinji Yoshida, Robert R. Graham, Arun Manoharan, Ward Ortmann, Tushar Bhangale, Joshua C. Denny, Robert J. Carroll, Anne E. Eyler, Jeffrey D. Greenberg, Joel M. Kremer, Dimitrios A. Pappas, Lei Jiang, Jian Yin, Lingying Ye, Ding-Feng Su, Jian Yang, Gang Xie, Ed Keystone, Harm-Jan Westra, Tõnu Esko, Andres Metspalu, Xuezhong Zhou, Namrata Gupta, Daniel Mirel, Eli A. Stahl, Dorothée Diogo, Jing Cui, Katherine Liao, Michael H. Guo, Keiko Myouzen, Takahisa Kawaguchi, Marieke J. H. Coenen, Piet L. C. M. van Riel, Mart A. F. J. van de Laar, Henk-Jan Guchelaar, Tom W. J. Huizinga, Philippe Dieudé, Xavier Mariette, S. Louis Bridges, Alexandra Zhernakova, Rene E. M. Toes, Paul P. Tak, Corinne Miceli-Richard, So-Young Bang, Hye-Soon Lee, Javier Martin, Miguel A. Gonzalez-Gay, Luis Rodriguez-Rodriguez, Solbritt Rantapää-Dahlqvist, Lisbeth Ärlestig, Hyon K. Choi, Yoichiro Kamatani, Pilar Galan, Mark Lathrop, Steve Eyre, John Bowes, Anne Barton, Niek de Vries, Larry W. Moreland, Lindsey A. Criswell, Elizabeth W. Karlson, Atsuo Taniguchi, Ryo Yamada, Michiaki Kubo, Jun S. Liu, Sang-Cheol Bae, Jane Worthington, Leonid Padyukov, Lars Klareskog, Peter K. Gregersen, Soumya Raychaudhuri, Barbara E. Stranger, Philip L. De Jager, Lude Franke, Peter M. Visscher, Matthew A. Brown, Hisashi Yamanaka, Tsuneyo Mimori, Atsushi Takahashi, Huji Xu, Timothy W. Behrens, Katherine A. Siminovitch, Shigeki Momohara, Fumihiko Matsuda, Kazuhiko Yamamoto and Robert M. Plenge ()
Additional contact information
Yukinori Okada: Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School
Di Wu: Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School
Gosia Trynka: Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School
Towfique Raj: Brigham and Women’s Hospital, Harvard Medical School
Chikashi Terao: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Katsunori Ikari: Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo 162-0054, Japan.
Yuta Kochi: Laboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Koichiro Ohmura: Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Akari Suzuki: Laboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Shinji Yoshida: Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo 162-0054, Japan.
Robert R. Graham: Immunology Biomarkers Group, Genentech
Arun Manoharan: Immunology Biomarkers Group, Genentech
Ward Ortmann: Immunology Biomarkers Group, Genentech
Tushar Bhangale: Immunology Biomarkers Group, Genentech
Joshua C. Denny: Vanderbilt University School of Medicine
Robert J. Carroll: Vanderbilt University School of Medicine
Anne E. Eyler: Vanderbilt University School of Medicine
Jeffrey D. Greenberg: New York University Hospital for Joint Diseases
Joel M. Kremer: Albany Medical Center and The Center for Rheumatology
Dimitrios A. Pappas: New York, Presbyterian Hospital, College of Physicians and Surgeons, Columbia University
Lei Jiang: Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Jian Yin: Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Lingying Ye: Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Ding-Feng Su: Second Military Medical University, Shanghai 200433, China.
Jian Yang: University of Queensland Diamantina Institute, Translational Research Institute
Gang Xie: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
Ed Keystone: Mount Sinai Hospital and University of Toronto, Toronto M5S 2J7, Canada.
Harm-Jan Westra: University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9700 RB, the Netherlands.
Tõnu Esko: Program in Medical and Population Genetics, Broad Institute
Andres Metspalu: Estonian Genome Center, University of Tartu, Riia 23b, Tartu 51010, Estonia.
Xuezhong Zhou: School of Computer and Information Technology, Beijing Jiaotong University, Beijing 100044, China.
Namrata Gupta: Program in Medical and Population Genetics, Broad Institute
Daniel Mirel: Program in Medical and Population Genetics, Broad Institute
Eli A. Stahl: The Department of Psychiatry at Mount Sinai School of Medicine
Dorothée Diogo: Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School
Jing Cui: Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School
Katherine Liao: Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School
Michael H. Guo: Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School
Keiko Myouzen: Laboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Takahisa Kawaguchi: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Marieke J. H. Coenen: Radboud University Medical Centre, Nijmegen 6500 HB, the Netherlands.
Piet L. C. M. van Riel: Radboud University Medical Centre, Nijmegen 6500 HB, the Netherlands.
Mart A. F. J. van de Laar: Arthritis Center Twente, University Twente & Medisch Spectrum Twente, Enschede 7500 AE, the Netherlands.
Henk-Jan Guchelaar: Leiden University Medical Center, Leiden 2300 RC, the Netherlands.
Tom W. J. Huizinga: Leiden University Medical Center, Leiden 2300 RC, the Netherlands.
Philippe Dieudé: Service de Rhumatologie et INSERM U699 Hôpital Bichat Claude Bernard, Assistance Publique des Hôpitaux de Paris, Paris 75018, France.
Xavier Mariette: Institut National de la Santé et de la Recherche Médicale (INSERM) U1012, Université Paris-Sud, Rhumatologie, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre 94275, France.
S. Louis Bridges: University of Alabama at Birmingham
Alexandra Zhernakova: University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9700 RB, the Netherlands.
Rene E. M. Toes: Leiden University Medical Center, Leiden 2300 RC, the Netherlands.
Paul P. Tak: AMC/University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Corinne Miceli-Richard: Institut National de la Santé et de la Recherche Médicale (INSERM) U1012, Université Paris-Sud, Rhumatologie, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre 94275, France.
So-Young Bang: Hanyang University Hospital for Rheumatic Diseases, Seoul 133-792, South Korea.
Hye-Soon Lee: Hanyang University Hospital for Rheumatic Diseases, Seoul 133-792, South Korea.
Javier Martin: Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Granada 18100, Spain.
Miguel A. Gonzalez-Gay: Hospital Marques de Valdecilla, IFIMAV, Santander 39008, Spain.
Luis Rodriguez-Rodriguez: Hospital Clinico San Carlos, Madrid 28040, Spain.
Solbritt Rantapää-Dahlqvist: Umeå University, Umeå SE-901 87, Sweden.
Lisbeth Ärlestig: Umeå University, Umeå SE-901 87, Sweden.
Hyon K. Choi: Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School
Yoichiro Kamatani: Centre d’Etude du Polymorphisme Humain (CEPH), Paris 75010, France.
Pilar Galan: Université Paris 13 Sorbonne Paris Cité, UREN (Nutritional Epidemiology Research Unit), Inserm (U557), Inra (U1125), Cnam, Bobigny 93017, France.
Mark Lathrop: McGill University and Génome Québec Innovation Centre, Montréal, Québec H3A 0G1 Canada.
Steve Eyre: Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9NT, UK.
John Bowes: Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9NT, UK.
Anne Barton: Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9NT, UK.
Niek de Vries: Academic Medical Center/University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Larry W. Moreland: University of Pittsburgh
Lindsey A. Criswell: Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco
Elizabeth W. Karlson: Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School
Atsuo Taniguchi: Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo 162-0054, Japan.
Ryo Yamada: Unit of Statistical Genetics, Center for Genomic Medicine Graduate School of Medicine Kyoto University, Kyoto 606-8507, Japan.
Michiaki Kubo: Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Jun S. Liu: Harvard University
Sang-Cheol Bae: Hanyang University Hospital for Rheumatic Diseases, Seoul 133-792, South Korea.
Jane Worthington: Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9NT, UK.
Leonid Padyukov: Rheumatology Unit, Karolinska Institutet, Stockholm SE-171 76, Sweden.
Lars Klareskog: Rheumatology Unit, Karolinska Institutet, Stockholm SE-171 76, Sweden.
Peter K. Gregersen: The Feinstein Institute for Medical Research, North Shore–Long Island Jewish Health System
Soumya Raychaudhuri: Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School
Barbara E. Stranger: Section of Genetic Medicine, University of Chicago
Philip L. De Jager: Brigham and Women’s Hospital, Harvard Medical School
Lude Franke: University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9700 RB, the Netherlands.
Peter M. Visscher: University of Queensland Diamantina Institute, Translational Research Institute
Matthew A. Brown: University of Queensland Diamantina Institute, Translational Research Institute
Hisashi Yamanaka: Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo 162-0054, Japan.
Tsuneyo Mimori: Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Atsushi Takahashi: Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Huji Xu: Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Timothy W. Behrens: Immunology Biomarkers Group, Genentech
Katherine A. Siminovitch: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
Shigeki Momohara: Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo 162-0054, Japan.
Fumihiko Matsuda: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Kazuhiko Yamamoto: Laboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Robert M. Plenge: Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School

Nature, 2014, vol. 506, issue 7488, 376-381

Abstract: A genome-wide association study meta-analysis of more than 100,000 subjects of European and Asian ancestries reveals 42 new risk loci for rheumatoid arthritis, with follow-up studies identifying 98 biological candidate genes that are either already being targeted by drugs or could be in the future.

Date: 2014
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DOI: 10.1038/nature12873

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