Evidence map›Paper›PMID 26598658›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis.

Michael J Ombrello, Elaine F Remmers, Ioanna Tachmazidou, Alexei Grom, Dirk Foell, Johannes-Peter Haas, Alberto Martini, Marco Gattorno, Seza Özen, Sampath Prahalad and 46 more

Open access · bronzeAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 1 pooled it
9.7field-weighted citation impact, top 2% 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

95 citing papers in PubMed, 1 synthesis or guideline pooled it, 179 citations in OpenAlex.

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35 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

56 authors at 20 institutions in 16 countries.

Michael J OmbrelloTranslational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892; ombrellomj@mail.nih.gov kastnerd@mail.nih.gov.
Elaine F RemmersInflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;
Ioanna TachmazidouHuman Genetics, The Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, United Kingdom;
Alexei GromDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229; Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229;
Dirk FoellDepartment of Pediatric Rheumatology and Immunology, University Hospital Münster, D-48149 Münster, Germany;
Johannes-Peter HaasGerman Center for Pediatric and Adolescent Rheumatology, 82467 Garmisch-Partenkirchen, Germany;
Alberto MartiniDepartment of Pediatrics, University of Genova, 16145 Genoa, Italy; Pediatrics II Unit, G. Gaslini Institute, 16147 Genoa, Italy;
Marco GattornoPediatrics II Unit, G. Gaslini Institute, 16147 Genoa, Italy;
Seza ÖzenDepartment of Pediatric Rheumatology, Hacettepe University, 06100 Ankara, Turkey;
Sampath PrahaladDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322;
Andrew S ZeftDepartment of Pediatrics, Cleveland Clinic, Cleveland, OH 44195;
John F BohnsackDepartment of Pediatrics, University of Utah, Salt Lake City, UT 84113;
Elizabeth D MellinsDepartment of Pediatrics, Stanford University, Stanford, CA 94305;
Norman T IlowiteDepartment of Pediatrics, Albert Einstein College of Medicine and Children's Hospital at Montefiore, Bronx, NY 10461;
Ricardo RussoService of Immunology and Rheumatology, Hospital de Pediatria Garrahan, C1245AAM Buenos Aires, Argentina;
Claudio LenDepartment of Pediatrics, Universidade Federal de São Paulo, São Paulo, 04021-001, Brazil;
Maria Odete E HilarioDepartment of Pediatrics, Universidade Federal de São Paulo, São Paulo, 04021-001, Brazil;
Sheila OliveiraUniversidade Federal de Rio de Janeiro, Rio de Janeiro, 21941-901, Brazil;
Rae S M YeungDepartment of Pediatrics, University of Toronto, Toronto, Canada M5S 1A8; Department of Immunology, University of Toronto, Toronto, Canada M5S 1A8; Institute of Medical Science, University of Toronto, Toronto, Canada M5S 1A8;
Alan RosenbergDepartment of Pediatrics, University of Saskatchewan, Saskatoon, Canada S7N 0W8;
Lucy R WedderburnInstitute of Child Health, University College London, London, WC1N 1EH, United Kingdom; Center of Paediatric and Adolescent Rheumatology, University College London, London, WC1N 1EH, United Kingdom;
Jordi AntonPediatric Rheumatology Unit, Hospital Sant Joan de Déu, Universitat de Barcelona, 08950 Barcelona, Spain;
Tobias SchwarzSection of Pediatric Rheumatology and Osteology, University of Würzberg, 97080 Würzberg, Germany;
Anne HinksArthritis Research UK Centre for Genetics and Genomics, Manchester Academic Health Centre, University of Manchester, Manchester, M13 9PT, United Kingdom;
Yelda BilginerDepartment of Pediatric Rheumatology, Hacettepe University, 06100 Ankara, Turkey;
Jane ParkDepartment of Pediatrics, Stanford University, Stanford, CA 94305;
Joanna CobbArthritis Research UK Centre for Genetics and Genomics, Manchester Academic Health Centre, University of Manchester, Manchester, M13 9PT, United Kingdom; National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit, Central Manchester National Health Service Foundation Trust, Manchester Academic Health Centre, University of Manchester, Manchester, M13 9PT, United Kingdom;
Colleen L SatoriusInflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;
Buhm HanMedical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142; Division of Immunology, Allergy, and Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; Department of Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, Republic of Korea;
Elizabeth BaskinTranslational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892;
Sara SignaDepartment of Pediatrics, University of Genova, 16145 Genoa, Italy;
Richard H DuerrDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA 15261; Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA 15261;
J P AchkarDepartment of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195; Department of Pathobiology, Cleveland Clinic, Cleveland, OH 44195;
M Ilyas KambohDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;
Kenneth M KaufmanDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229; Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229;
Leah C KottyanDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229; Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229;
Dalila PintoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine At Mount Sinai, New York, NY 10029;
Stephen W SchererThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada;
Marta E Alarcón-RiquelmeArthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104; Center for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Government, PTS Granada 18016, Spain;
Elisa DocampoInterdisciplinary Cluster for Applied Genoproteomics-Université de Liège, 4000-Liège, Belgium; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, and Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain;
Xavier EstivillCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, and Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain;
Ahmet GülIstanbul Faculty of Medicine, Istanbul University, 34390 Istanbul, Turkey;
British Society of Pediatric and Adolescent Rheumatology (BSPAR) Study Group
Childhood Arthritis Prospective Study (CAPS) Group
Randomized Placebo Phase Study of Rilonacept in sJIA (RAPPORT) Investigators
Sparks-Childhood Arthritis Response to Medication Study (CHARMS) Group
Biologically Based Outcome Predictors in JIA (BBOP) Group
Paul I W de BakkerDepartment of Epidemiology, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands; and.
Soumya RaychaudhuriArthritis Research UK Centre for Genetics and Genomics, Manchester Academic Health Centre, University of Manchester, Manchester, M13 9PT, United Kingdom; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142; Division of Immunology, Allergy, and Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
Carl D LangefeldDepartment of Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, NC 27106.
Susan ThompsonDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229; Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229;
Eleftheria ZegginiHuman Genetics, The Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, United Kingdom;
Wendy ThomsonArthritis Research UK Centre for Genetics and Genomics, Manchester Academic Health Centre, University of Manchester, Manchester, M13 9PT, United Kingdom; National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit, Central Manchester National Health Service Foundation Trust, Manchester Academic Health Centre, University of Manchester, Manchester, M13 9PT, United Kingdom;
Daniel L KastnerInflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; ombrellomj@mail.nih.gov kastnerd@mail.nih.gov.
Patricia WooCenter of Paediatric and Adolescent Rheumatology, University College London, London, WC1N 1EH, United Kingdom;
International Childhood Arthritis Genetics (INCHARGE) Consortium
Manchester Academic Health Science Centre · GBUniversity of Liverpool · GBCincinnati Children's Hospital Medical Center · USHospital for Sick Children · CANational Institutes of Health · USRoyal Hospital for Children · GBChildren's Hospital of Eastern Ontario · CACleveland Clinic · USNational Health Service · GBBroad Institute · USCity, University of London · GBIzaak Walton Killam Health Centre · CAUniversity of Saskatchewan · CAAlbert Einstein College of Medicine · USGreat Ormond Street Hospital · GBThe University of Sydney · AUBirmingham Children's Hospital · GBWellcome Sanger Institute · GBBC Children's Hospital · CARoyal Victoria Infirmary · GB

Funding

TREATMENT OF DEPRESSION IN ALZHEIMER'S DISEASEP50AG005133 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BECKER, JAMES T. · 1985 to 2019
$43.0M
LCenter for Clinical and Translational Science and TrainingUL1TR001425 · NCATS · UNIVERSITY OF CINCINNATI · PI HEUBI, JAMES E., KISSELA, BRETT M · 2015 to 2024
$37.5M
Core-010UL1TR001073 · NCATS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI KELLER, MARLA J, SHAMOON, HARRY · 2013 to 2017
$21.3M
Genetic Analysis of Complex Inflammatory DisordersZIAHG200371 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI KASTNER, DANIEL · 2011 to 2024
$18.8M
Genetics and pathophysiology of systemic juvenile idiopathic arthritis and other complex autoinflammatory diseasesZIAAR041198 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI OMBRELLO, MICHAEL · 2014 to 2025
$14.4M
ROLE OF ANGPTL4, AN ANGIOGENIC MEDIATOR, IN ARTHRITISP30AR047363 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI THOMPSON, SUSAN D · 2001 to 2015
$9.2M
NIDDK IBD Genetics Consortium Genetic Research CenterU01DK062420 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DUERR, RICHARD H · 2002 to 2021
$7.8M
Search for the Alzheimers GenesR01AG030653 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KAMBOH, M. ILYAS · 2009 to 2019
$7.7M
Training Program in Adult and Pediatric RheumatologyT32AR050942 · NIAMS · STANFORD UNIVERSITY · PI LEWIS, DAVID BRAM, ROBINSON, WILLIAM H · 2005 to 2025
$6.6M
RA-SLE Molecular Deconstruction Leadership CenterUH2AR067677 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI BRENNER, MICHAEL B., RAYCHAUDHURI, SOUMYA · 2014 to 2020
$4.3M
Deep Resequencing of Candidate Gene Regions in Late-onset Alzheimer's DiseaseR01AG041718 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KAMBOH, M. ILYAS · 2012 to 2016
$3.0M
Genetics and Pathophysiology of Systemic Onset Juvenile Idiopathic ArthritisZIAHG200370 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI KASTNER, DANIEL · 2011 to 2013
$2.2M
Arthritis Research UK 20385Arthritis Research UK 20386Arthritis Research UK 20542Intramural NIH HHS Z99 AR999999Intramural NIH HHS ZIA AR041198Medical Research Council MR/M004600/1NCATS NIH HHS UL1 TR001073NCATS NIH HHS UL1 TR001425NHGRI NIH HHS Z01-HG200370NIAMS NIH HHS N1R01-AR062886NIAMS NIH HHS P30 AR047363NIAMS NIH HHS R01 AR059049NIAMS NIH HHS R01-AR059049NIAMS NIH HHS R01 AR060893NIAMS NIH HHS R01-AR060893NIAMS NIH HHS R01 AR062886NIAMS NIH HHS RC1 AR058587NIAMS NIH HHS T32 AR050942NIAMS NIH HHS UH2 AR067677NIAMS NIH HHS Z01-AR041198NIA NIH HHS AG005133NIA NIH HHS AG030653NIA NIH HHS AG041718NIA NIH HHS P50 AG005133NIA NIH HHS R01 AG030653NIA NIH HHS R01 AG041718NIDDK NIH HHS R01 DK076025NIDDK NIH HHS R01-DK076025NIDDK NIH HHS U01 DK062420NIDDK NIH HHS U01-DK062420Versus Arthritis 20386Versus Arthritis 20542Wellcome Trust 076113Wellcome Trust 085475Wellcome Trust 098051
6 · The paper itself

Abstract

Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 [P = 2.8 × 10(-17), odds ratio (OR) 2.6 (2.1, 3.3)], was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk [P = 1.0 × 10(-5), OR 0.7 (0.6, 0.8)]. Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [P = 2.7 × 10(-16), OR 2.3 (1.9, 2.8)], as was the HLA-DRB1*11-HLA-DQA1*05-HLA-DQB1*03 haplotype [6.4 × 10(-17), OR 2.3 (1.9, 2.9)]. By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA.

Indexed as

Polymorphism, Single NucleotideArthritis, JuvenileChildGene FrequencyGenetic Predisposition to DiseaseGenotypeHaplotypesHistocompatibility Antigens Class IIHLA-DRB1 ChainsHumansLinkage DisequilibriumMeta-Analysis as TopicOdds RatioRisk FactorsHistocompatibility Antigens Class IIHLA-DRB1 Chainsautoinflammationhuman leukocyte antigenStill’s diseasesystemic juvenile idiopathic arthritis

Identifiers

PMID26598658
PMCPMC4702958
OpenAlexW2179196974

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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.