Evidence map›Paper›PMID 24390342›Full record

SynthesisNature2014

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 and 87 more

Open access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,359 papers, 16 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,359citing papers in PubMed, 16 pooled it
127.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1,359 citing papers in PubMed, 16 syntheses or guidelines pooled it, 2,443 citations in OpenAlex.

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1,299 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

97 authors at 20 institutions in 12 countries.

Yukinori Okada1] Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA.
Di Wu1] Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [4] Department of Statistics, Harvard University, Cambridge, Massachusetts 02138, USA. [5] Centre for Cancer Research, Monash Institute of Medical Research, Monash University, Clayton, Victoria 3800, Australia.
Gosia Trynka1] Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA.
Towfique Raj1] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [3] Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Chikashi Terao1] Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan. [2] Department of Rheumatology and Clinical immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Katsunori IkariInstitute of Rheumatology, Tokyo Women's Medical University, Tokyo 162-0054, Japan.
Yuta KochiLaboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Koichiro OhmuraDepartment of Rheumatology and Clinical immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Akari SuzukiLaboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Shinji YoshidaInstitute of Rheumatology, Tokyo Women's Medical University, Tokyo 162-0054, Japan.
Robert R GrahamImmunology Biomarkers Group, Genentech, South San Francisco, California 94080, USA.
Arun ManoharanImmunology Biomarkers Group, Genentech, South San Francisco, California 94080, USA.
Ward OrtmannImmunology Biomarkers Group, Genentech, South San Francisco, California 94080, USA.
Tushar BhangaleImmunology Biomarkers Group, Genentech, South San Francisco, California 94080, USA.
Joshua C Denny1] Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. [2] Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Robert J CarrollDepartment of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Anne E EylerDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Jeffrey D GreenbergNew York University Hospital for Joint Diseases, New York, New York 10003, USA.
Joel M KremerDepartment of Medicine, Albany Medical Center and The Center for Rheumatology, Albany, New York 12206, USA.
Dimitrios A PappasDivision of Rheumatology, Department of Medicine, New York, Presbyterian Hospital, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Lei JiangDepartment of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Jian YinDepartment of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Lingying YeDepartment of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Ding-Feng SuDepartment of Pharmacology, Second Military Medical University, Shanghai 200433, China.
Jian Yang1] University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland 4072, Australia. [2] Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
Gang Xie1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. [2] Toronto General Research Institute, Toronto, Ontario M5G 2M9, Canada. [3] Department of Medicine, University of Toronto, Toronto, Ontario M5S 2J7, Canada.
Ed KeystoneDepartment of Medicine, Mount Sinai Hospital and University of Toronto, Toronto M5S 2J7, Canada.
Harm-Jan WestraDepartment of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9700 RB, the Netherlands.
Tõnu Esko1] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [2] Estonian Genome Center, University of Tartu, Riia 23b, Tartu 51010, Estonia. [3] Division of Endocrinology, Children's Hospital, Boston, Massachusetts 02115, USA.
Andres MetspaluEstonian Genome Center, University of Tartu, Riia 23b, Tartu 51010, Estonia.
Xuezhong ZhouSchool of Computer and Information Technology, Beijing Jiaotong University, Beijing 100044, China.
Namrata GuptaProgram in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA.
Daniel MirelProgram in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA.
Eli A StahlThe Department of Psychiatry at Mount Sinai School of Medicine, New York, New York 10029, USA.
Dorothée Diogo1] Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA.
Jing Cui1] Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA.
Katherine Liao1] Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA.
Michael H Guo1] Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [3] Division of Endocrinology, Children's Hospital, Boston, Massachusetts 02115, USA.
Keiko MyouzenLaboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Takahisa KawaguchiCenter for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Marieke J H CoenenDepartment of Human Genetics, Radboud University Medical Centre, Nijmegen 6500 HB, the Netherlands.
Piet L C M van RielDepartment of Rheumatology, Radboud University Medical Centre, Nijmegen 6500 HB, the Netherlands.
Mart A F J van de LaarDepartment of Rheumatology and Clinical Immunology, Arthritis Center Twente, University Twente & Medisch Spectrum Twente, Enschede 7500 AE, the Netherlands.
Henk-Jan GuchelaarDepartment of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden 2300 RC, the Netherlands.
Tom W J HuizingaDepartment of Rheumatology, Leiden University Medical Center, Leiden 2300 RC, the Netherlands.
Philippe Dieudé1] Service de Rhumatologie et INSERM U699 Hôpital Bichat Claude Bernard, Assistance Publique des Hôpitaux de Paris, Paris 75018, France. [2] Université Paris 7-Diderot, Paris 75013, France.
Xavier MarietteInstitut 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 BridgesDivision of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Alexandra Zhernakova1] Department of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9700 RB, the Netherlands. [2] Department of Rheumatology, Leiden University Medical Center, Leiden 2300 RC, the Netherlands.
Rene E M ToesDepartment of Rheumatology, Leiden University Medical Center, Leiden 2300 RC, the Netherlands.
Paul P Tak1] AMC/University of Amsterdam, Amsterdam 1105 AZ, the Netherlands. [2] GlaxoSmithKline, Stevenage SG1 2NY, UK. [3] University of Cambridge, Cambridge CB2 1TN, UK.
Corinne Miceli-RichardInstitut 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 BangDepartment of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 133-792, South Korea.
Hye-Soon LeeDepartment of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 133-792, South Korea.
Javier MartinInstituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Granada 18100, Spain.
Miguel A Gonzalez-GayDepartment of Rheumatology, Hospital Marques de Valdecilla, IFIMAV, Santander 39008, Spain.
Luis Rodriguez-RodriguezHospital Clinico San Carlos, Madrid 28040, Spain.
Solbritt Rantapää-Dahlqvist1] Department of Public Health and Clinical Medicine, Umeå University, Umeå SE-901 87, Sweden. [2] Department of Rheumatology, Umeå University, Umeå SE-901 87, Sweden.
Lisbeth Arlestig1] Department of Public Health and Clinical Medicine, Umeå University, Umeå SE-901 87, Sweden. [2] Department of Rheumatology, Umeå University, Umeå SE-901 87, Sweden.
Hyon K Choi1] Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02115, Massachusetts, USA. [2] Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. [3] Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Yoichiro KamataniCentre d'Etude du Polymorphisme Humain (CEPH), Paris 75010, France.
Pilar GalanUniversité Paris 13 Sorbonne Paris Cité, UREN (Nutritional Epidemiology Research Unit), Inserm (U557), Inra (U1125), Cnam, Bobigny 93017, France.
Mark LathropMcGill University and Génome Québec Innovation Centre, Montréal, Québec H3A 0G1 Canada.
RACI consortium
GARNET consortium
Steve Eyre1] Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9NT, UK. [2] National Institute for Health Research, Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals National Health Service Foundation Trust, Manchester Academic Health Sciences Centre, Manchester M13 9NT, UK.
John Bowes1] Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9NT, UK. [2] National Institute for Health Research, Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals National Health Service Foundation Trust, Manchester Academic Health Sciences Centre, Manchester M13 9NT, UK.
Anne BartonArthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9NT, UK.
Niek de VriesDepartment of Clinical Immunology and Rheumatology & Department of Genome Analysis, Academic Medical Center/University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Larry W MorelandDivision of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Lindsey A CriswellRosalind Russell Medical Research Center for Arthritis, Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, California 94117, USA.
Elizabeth W KarlsonDivision of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Atsuo TaniguchiInstitute of Rheumatology, Tokyo Women's Medical University, Tokyo 162-0054, Japan.
Ryo YamadaUnit of Statistical Genetics, Center for Genomic Medicine Graduate School of Medicine Kyoto University, Kyoto 606-8507, Japan.
Michiaki KuboLaboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Jun S LiuDepartment of Statistics, Harvard University, Cambridge, Massachusetts 02138, USA.
Sang-Cheol BaeDepartment of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 133-792, South Korea.
Jane Worthington1] Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9NT, UK. [2] National Institute for Health Research, Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals National Health Service Foundation Trust, Manchester Academic Health Sciences Centre, Manchester M13 9NT, UK.
Leonid PadyukovRheumatology Unit, Department of Medicine (Solna), Karolinska Institutet, Stockholm SE-171 76, Sweden.
Lars KlareskogRheumatology Unit, Department of Medicine (Solna), Karolinska Institutet, Stockholm SE-171 76, Sweden.
Peter K GregersenThe Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York 11030, USA.
Soumya Raychaudhuri1] Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [4] NIHR Manchester Musculoskeletal Biomedical, Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester M13 9NT, UK.
Barbara E Stranger1] Section of Genetic Medicine, University of Chicago, Chicago, Illinois 60637, USA. [2] Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois 60637, USA.
Philip L De Jager1] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA. [3] Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Lude FrankeDepartment of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9700 RB, the Netherlands.
Peter M Visscher1] University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland 4072, Australia. [2] Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
Matthew A BrownUniversity of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland 4072, Australia.
Hisashi YamanakaInstitute of Rheumatology, Tokyo Women's Medical University, Tokyo 162-0054, Japan.
Tsuneyo MimoriDepartment of Rheumatology and Clinical immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Atsushi TakahashiLaboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Huji XuDepartment of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Timothy W BehrensImmunology Biomarkers Group, Genentech, South San Francisco, California 94080, USA.
Katherine A Siminovitch1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. [2] Toronto General Research Institute, Toronto, Ontario M5G 2M9, Canada. [3] Department of Medicine, University of Toronto, Toronto, Ontario M5S 2J7, Canada.
Shigeki MomoharaInstitute of Rheumatology, Tokyo Women's Medical University, Tokyo 162-0054, Japan.
Fumihiko Matsuda1] Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan. [2] Core Research for Evolutional Science and Technology (CREST) program, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan. [3] Institut National de la Sante et de la Recherche Medicale (INSERM) Unite U852, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Kazuhiko Yamamoto1] Laboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan. [2] Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo 113-0033, Japan.
Robert M Plenge1] Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA.
Broad Institute · USRIKEN Center for Integrative Medical Sciences · JPHarvard University · USKyoto University · JPTokyo Women's Medical University · JPBrigham and Women's Hospital · USHanyang University Seoul Hospital · KRLeiden University Medical Center · NLSecond Military Medical University · CNUniversity Medical Center Groningen · NLVanderbilt University · USKarolinska Institutet · SEManchester Academic Health Science Centre · GBShanghai Changzheng Hospital · CNTranslational Research Institute · AUUmeå University · SEUniversity of Amsterdam · NLUniversity of Manchester · GBUniversity of Toronto · CABeijing Jiaotong University · CN

Funding

Vanderbilt Biomedical Informatics Training ProgramT15LM007450 · NLM · VANDERBILT UNIVERSITY · PI Jessica S. Ancker, Bradley A. Malin · 2002 to 2026
$19.7M
WORK DISABILITY-- PERSONS WITH RHEUMATOID ARTHRITISP60AR047785 · NIAMS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FELSON, DAVID TOBIN · 2001 to 2016
$18.0M
Pharmacogenomics of Arrhythmia TherapyU19HL065962 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RODEN, DAN M · 2010 to 2014
$17.4M
Genetic predictors of response to anti-TNF therapy in rheumatoid arthritisU01GM092691 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI BRENNER, MICHAEL B., RAYCHAUDHURI, SOUMYA · 2010 to 2014
$7.5M
Discovery and Functional Impact of Common and Rare Variants in RAR01AR063759 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Soumya Raychaudhuri · 2013 to 2026
$5.4M
NOVEL METABOLITE AND MICROBIOTA PATHWAYS FOR HYPERURICEMIA AND GOUTR01AR065944 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI CHOI, HYON K · 2013 to 2025
$4.2M
Genetics of GoutR01AR056291 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI CHOI, HYON K · 2008 to 2011
$2.9M
Dissection of two rheumatoid arthritis risk loci from genome-wide studiesR01AR056768 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI BRENNER, MICHAEL B. · 2009 to 2013
$1.9M
Genetic Predictors of Early Atherosclerosis in SLEK24AR052403 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI KARLSON, ELIZABETH W · 2005 to 2014
$1.5M
Genetic Risk Factors for Coronary Artery Disease in Rheumatoid ArthritisK08AR060257 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI LIAO, KATHERINE PHOENIX · 2011 to 2015
$649k
Meta-analysis of GWAS data to identify novel rheumatoid arthritis risk lociR01AR057108 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI PLENGE, ROBERT M · 2009 to 2010
$557k
Deep Re-Sequencing of Rheumatoid Arthritis Risk LociR01AR059648 · NIAMS · BROAD INSTITUTE, INC. · PI PLENGE, ROBERT M · 2010 to 2011
$493k
Arthritis Research UK 20385CIHR 79321Department of Health MANMKBRU-2012-1NHLBI NIH HHS U19 HL065962NIAMS NIH HHS K08 AR060257NIAMS NIH HHS K24 AR052403NIAMS NIH HHS P60 AR047785NIAMS NIH HHS R01-AR056291NIAMS NIH HHS R01 AR056768NIAMS NIH HHS R01-AR056768NIAMS NIH HHS R01 AR057108NIAMS NIH HHS R01-AR057108NIAMS NIH HHS R01 AR059648NIAMS NIH HHS R01-AR059648NIAMS NIH HHS R01 AR063759NIAMS NIH HHS R01AR063759-01A1NIAMS NIH HHS R01-AR065944NIAMS NIH HHS R21 AR056042NIGMS NIH HHS U01 GM092691NIGMS NIH HHS U01-GM092691NLM NIH HHS T15 LM007450PHS HHS K08-KAR055688A
6 · The paper itself

Abstract

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ∼10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2 - 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation, cis-acting expression quantitative trait loci and pathway analyses--as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes--to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.

Indexed as

Drug DiscoveryMolecular Targeted TherapyAllelesAnimalsArthritis, RheumatoidAsian PeopleCase-Control StudiesComputational BiologyDrug RepositioningFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHematologic NeoplasmsHumansMaleMice

Identifiers

PMID24390342
PMCPMC3944098
OpenAlexW1989590412

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.