ArticleAnnals of the rheumatic diseases2017
Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications.
Registry-linked trialOpen access · hybridAbstract read
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Article in Annals of the rheumatic diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06356350 (Effects of Exercise Programs on Gait in Children With Juvenile Idiopathic Arthritis), which is not on this map. Cited by 85 papers, 5 of them syntheses that pooled it.
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85citing papers in PubMed, 5 pooled it
12.7field-weighted citation impact, top 1% of its field
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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.
Effects of Exercise Programs on Gait in Children With Juvenile Idiopathic Arthritis
Who cites it
85 citing papers in PubMed, 5 syntheses or guidelines pooled it, 160 citations in OpenAlex.
- Is a variant of uncertain significance always 'insignificant'? A systematic review on PRF1 A91V in Hemophagocytic Lymphohistocytosis and comparative analysis with Still's disease.Orphanet journal of rare diseases · 2026Pooled it
- Efficacy of biologic DMARDs in improving the clinical response of patients with polyarticular juvenile idiopathic arthritis: a meta-analysis of RCTs.Advances in rheumatology (London, England) · 2025Pooled it
- Is There a Link between the Molecular Basis of Juvenile Idiopathic Arthritis and Autoimmune Diseases? Systematic Review.International journal of molecular sciences · 2024Pooled it
- 2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2022Guideline
- 2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis.Arthritis care & research · 2022Guideline
- Gut microbiota in children with juvenile idiopathic arthritis: characteristics, biomarker identification, and usefulness in clinical prediction.BMC genomics · 2020Trial
- Rare variant analysis of whole genome sequenced juvenile idiopathic arthritis multiplex pedigrees identifies rare variants in NOD2 and ACVR1.G3 (Bethesda, Md.) · 2026Article
- Baseline Clinical Features and Biomarker Profiles of the Childhood Arthritis and Rheumatology Research Alliance Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease Cohort.Arthritis care & research · 2026Article
- The Intertwining Between Arthritis and Inborn Errors of Immunity.Journal of clinical medicine · 2026Review
- Pathogenic and genetic landscape of Still's disease across ages, with new insights into age-related IL-18 patterns.Arthritis research & therapy · 2026Review
- Characterization of fibroblast-like synoviocytes from the synovial fluid of patients affected by juvenile idiopathic arthritis.Rheumatology (Oxford, England) · 2025Article
- Associations of Lymphocyte Subpopulations, Related Cytokines, Clinical Phenotypes, and Outcomes in Systemic Juvenile Idiopathic Arthritis.ACR open rheumatology · 2025Article
- Global burden and genetic insights of RA and JIA in ages 0-19 years: GBD 2021 and MR analysis.Frontiers in immunology · 2025Article
- Characteristics That Predict Psoriatic Arthritis by the Classification Criteria for Psoriatic Arthritis in Patients With Juvenile Idiopathic Arthritis 18 Years After Disease Onset.ACR open rheumatology · 2025Article
- Enrichment of Rare Variants of Hemophagocytic Lymphohistiocytosis Genes in Systemic Juvenile Idiopathic Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- New discoveries in the genetics and genomics of systemic juvenile idiopathic arthritis.Expert review of clinical immunology · 2024Review
- Initial Respiratory System Involvement in Juvenile Idiopathic Arthritis with Systemic Onset Is a Marker of Interstitial Lung Disease: The Results of Retrospective Cohort Study Analysis.Journal of clinical medicine · 2024Article
- Large-scale integrative analysis of juvenile idiopathic arthritis for new insight into its pathogenesis.Arthritis research & therapy · 2024Article
- Establishment and analysis of a novel diagnostic model for systemic juvenile idiopathic arthritis based on machine learning.Pediatric rheumatology online journal · 2024Article
- Autoinflammatory Contributors to Cytokine Storm.Advances in experimental medicine and biology · 2024Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
50 authors at 20 institutions in 12 countries.
Michael J OmbrelloTranslational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Victoria L ArthurTranslational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Elaine F RemmersInflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Anne HinksArthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, Manchester, UK.
Ioanna TachmazidouHuman Genetics, The Wellcome Trust Sanger Institute, Hinxton, UK.
Alexei A GromDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Dirk FoellDepartment of Pediatric Rheumatology and Immunology, University Hospital Münster, Münster, Germany.
Alberto MartiniDepartment of Pediatrics, University of Genova, Genoa, Italy.
Marco GattornoPediatrics II Unit, Giannina Gaslini Institute, Genoa, Italy.
Seza ÖzenDepartment of Pediatric Rheumatology, Hacettepe University, Ankara, Turkey.
Sampath PrahaladDepartments of Pediatrics and Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Andrew S ZeftDepartment of Pediatrics, Cleveland Clinic, Cleveland, Ohio, USA.
John F BohnsackDepartment of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
Norman T IlowiteDepartment of Pediatrics, Albert Einstein College of Medicine and Children's Hospital at Montefiore, Bronx, New York, USA.
Elizabeth D MellinsDepartment of Pediatrics, Stanford University, Stanford, California, USA.
Ricardo RussoService of Immunology and Rheumatology, Hospital de Pediatria Garrahan, Buenos Aires, Argentina.
Claudio LenDepartment of Pediatrics, Universidade Federal de São Paulo, São Paulo, Brazil.
Maria Odete E HilarioDepartment of Pediatrics, Universidade Federal de São Paulo, São Paulo, Brazil.
Sheila OliveiraUniversidade Federal de Rio de Janeiro, Rio de Janeiro, Brazil.
Rae S M YeungDepartment of Pediatrics, University of Toronto, Toronto, Canada.
Alan M RosenbergDepartment of Pediatrics, University of Saskatchewan, Saskatoon, Canada.
Lucy R WedderburnInstitute of Child Health, University College London, London, UK.
Jordi AntonPediatric Rheumatology Unit, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
Johannes-Peter HaasGerman Center for Pediatric and Adolescent Rheumatology, Garmisch-Partenkirchen, Germany.
Angela Rosen-WolffUniversity Hospital Cal Gustav Carus, Dresden, Germany.
Kirsten MindenDepartment of Rheumatology and Clinical Immunology, Charité -University Medicine, Berlin, Germany.
Klaus TenbrockDepartment of Pediatrics, RWTH Aachen University, Aachen, Germany.
Erkan DemirkayaDepartment of Pediatric Rheumatology, Hacettepe University, Ankara, Turkey.
Joanna CobbArthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, Manchester, UK.
Elizabeth BaskinTranslational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Sara SignaDepartment of Pediatrics, University of Genova, Genoa, Italy.
Emily ShuldinerTranslational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Richard H DuerrDepartment of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Jean-Paul AchkarDepartment of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA.
M Ilyas KambohDepartment of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Kenneth M KaufmanDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Leah C KottyanDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.ORCID http://orcid.org/0000-0003-3979-2220
Dalila PintoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Stephen W SchererThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Marta E Alarcón-RiquelmeCenter for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Government, Granada, Spain.
Elisa DocampoInterdisciplinary Cluster for Applied Genoproteomics-Université de Liège, Liège, Belgium.
Xavier EstivillCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, and Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Ahmet GülIstanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
British Society of Pediatric and Adolescent Rheumatology (BSPAR) Study Group, Inception Cohort of Newly Diagnosed Patients with Juvenile Idiopathic Arthritis (ICON-JIA) 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
Carl D LangefeldDepartment of Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA.
Susan ThompsonDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Eleftheria ZegginiHuman Genetics, The Wellcome Trust Sanger Institute, Hinxton, UK.
Daniel L KastnerInflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Patricia WooCenter of Paediatric and Adolescent Rheumatology, University College London, London, UK.
Wendy ThomsonArthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, Manchester, UK.
National Institutes of Health · USCincinnati Children's Hospital Medical Center · USManchester Academic Health Science Centre · GBCleveland Clinic · USHacettepe University · TRIstituto Giannina Gaslini · ITUniversidade Federal de São Paulo · BRUniversity College London · GBUniversity of Pittsburgh · USWellcome Sanger Institute · GBAlbert Einstein College of Medicine · USEmory University · USGarrahan Hospital · ARGerman Center for Pediatric and Adolescent Rheumatology · DEGerman Rheumatism Research Centre · DEHospital for Sick Children · CAHospital Sant Joan de Déu Barcelona · ESIcahn School of Medicine at Mount Sinai · USIstanbul University · TRKarolinska Institutet · SE
Funding
TREATMENT OF DEPRESSION IN ALZHEIMER'S DISEASEP50AG005133 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BECKER, JAMES T. · 1985 to 2019
$43.0MGenetic Analysis of Complex Inflammatory DisordersZIAHG200371 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI KASTNER, DANIEL · 2011 to 2024
$18.8MGenetics 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
$14.4MPediatric Rheumatology Tissue RepostoryP01AR048929 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI THOMPSON, SUSAN D · 2003 to 2015
$13.6MROLE OF ANGPTL4, AN ANGIOGENIC MEDIATOR, IN ARTHRITISP30AR047363 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI FLICK, MATTHEW J. · 2001 to 2015
$9.2MNIDDK IBD Genetics Consortium Genetic Research CenterU01DK062420 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DUERR, RICHARD H · 2002 to 2021
$7.8MTissue Repository CoreP30AR070549 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI Leah Claire Kottyan · 2016 to 2026
$7.7MSearch for the Alzheimers GenesR01AG030653 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KAMBOH, M. ILYAS · 2009 to 2019
$7.7MDeep Resequencing of Candidate Gene Regions in Late-onset Alzheimer's DiseaseR01AG041718 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KAMBOH, M. ILYAS · 2012 to 2016
$3.0MMUNC13-4 gene Polymorphisms in Macrophage Activation syndrome and Systemic JuveniR01AR059049 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI GROM, ALEXEI A · 2011 to 2015
$1.7MSegmental chromosome sharing in affected relatives with Juvenile ArthritisR01AR060893 · NIAMS · EMORY UNIVERSITY · PI PRAHALAD, SAMPATH · 2011 to 2014
$1.5MA role for IL-1 in SJIA monocyte phenotypes: A RAPPORT ancillary studyR01AR061297 · NIAMS · STANFORD UNIVERSITY · PI MELLINS, ELIZABETH D · 2010 to 2013
$1.2MIntramural NIH HHS Z99 AR999999NIAMS NIH HHS P01 AR048929NIAMS NIH HHS P30 AR047363NIAMS NIH HHS P30 AR070549NIAMS NIH HHS R01 AR059049NIAMS NIH HHS R01 AR060893NIAMS NIH HHS R01 AR061297NIA NIH HHS P50 AG005133NIA NIH HHS R01 AG030653NIA NIH HHS R01 AG041718NIDDK NIH HHS R01 DK076025NIDDK NIH HHS U01 DK062420Versus Arthritis 20542Wellcome Trust
Abstract
objectivesJuvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA.
methodsWe performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes.
resultsThe major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes.
conclusionsThe lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways.
Indexed as
Arthritis, JuvenileCase-Control StudiesChromosomes, Human, Pair 1Genome-Wide Association StudyGenotypeHumansMajor Histocompatibility ComplexPolymorphism, Single NucleotideRisk FactorsAdult Onset Still's DiseaseGene PolymorphismJuvenile Idiopathic Arthritis
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Registered trials
NCT06356350ClinicalTrials.gov
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.