Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications

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dc.citation.issue5
dc.citation.volume76
dc.contributor.authorOmbrello, Michael J.
dc.contributor.authorArthur, Victoria L.
dc.contributor.authorRemmers, Elaine F.
dc.contributor.authorHinks, Anne
dc.contributor.authorTachmazidou, Ioanna
dc.contributor.authorGrom, Alexei A.
dc.contributor.authorFoell, Dirk
dc.contributor.authorMartini, Alberto
dc.contributor.authorGattorno, Marco
dc.contributor.authorOzen, Seza
dc.contributor.authorPrahalad, Sampath
dc.contributor.authorZeft, Andrew S.
dc.contributor.authorBohnsack, John F.
dc.contributor.authorIlowite, Norman T.
dc.contributor.authorMellins, Elizabeth D.
dc.contributor.authorRusso, Ricardo
dc.contributor.authorLen, Claudio [UNIFESP]
dc.contributor.authorHilario, Maria Odete E. [UNIFESP]
dc.contributor.authorOliveira, Sheila
dc.contributor.authorYeung, Rae S. M.
dc.contributor.authorRosenberg, Alan M.
dc.contributor.authorWedderburn, Lucy R.
dc.contributor.authorAnton, Jordi
dc.contributor.authorHaas, Johannes-Peter
dc.contributor.authorRosen-Wolff, Angela
dc.contributor.authorMinden, Kirsten
dc.contributor.authorTenbrock, Klaus
dc.contributor.authorDemirkaya, Erkan
dc.contributor.authorCobb, Joanna
dc.contributor.authorBaskin, Elizabeth
dc.contributor.authorSigna, Sara
dc.contributor.authorShuldiner, Emily
dc.contributor.authorDuerr, Richard H.
dc.contributor.authorAchkar, Jean-Paul
dc.contributor.authorKamboh, M. Ilyas
dc.contributor.authorKaufman, Kenneth M.
dc.contributor.authorKottyan, Leah C.
dc.contributor.authorPinto, Dalila
dc.contributor.authorScherer, Stephen W.
dc.contributor.authorAlarcon-Riquelme, Marta E.
dc.contributor.authorDocampo, Elisa
dc.contributor.authorEstivill, Xavier
dc.contributor.authorGul, Ahmet
dc.contributor.authorLangefeld, Carl D.
dc.contributor.authorThompson, Susan
dc.contributor.authorZeggini, Eleftheria
dc.contributor.authorKastner, Daniel L.
dc.contributor.authorWoo, Patricia
dc.contributor.authorThomson, Wendy
dc.coverageLondon
dc.date.accessioned2020-07-17T14:02:14Z
dc.date.available2020-07-17T14:02:14Z
dc.date.issued2017
dc.description.abstractObjectives Juvenile 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. Methods We 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. Results The 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. Conclusions The 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.en
dc.description.affiliationNatl Inst Arthrit & Musculoskeletal & Skin Dis, Natl Inst Hlth, US Dept Hlth & Human Serv, Translat Genet & Genom Unit, Bethesda, MD USA
dc.description.affiliationNHGRI, Natl Inst Hlth, Inflammatory Dis Sect, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA
dc.description.affiliationManchester Acad Hlth Sci Ctr, Arthrit Res UK Ctr Genet & Genom, Ctr Musculoskeletal Res, Manchester, Lancs, England
dc.description.affiliationWellcome Trust Sanger Inst, Human Genet, Hinxton, England
dc.description.affiliationUniv Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA
dc.description.affiliationCincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA
dc.description.affiliationUniv Hosp Munster, Dept Pediat Rheumatol & Immunol, Munster, Germany
dc.description.affiliationUniv Genoa, Dept Pediat, Genoa, Italy
dc.description.affiliationGiannina Gaslini Inst, Pediat Unit 2, Genoa, Italy
dc.description.affiliationHacettepe Univ, Dept Pediat Rheumatol, Ankara, Turkey
dc.description.affiliationEmory Univ, Sch Med, Dept Pediat & Human Genet, Atlanta, GA 30322 USA
dc.description.affiliationChildrens Healthcare Atlanta, Atlanta, GA USA
dc.description.affiliationCleveland Clin, Dept Pediat, Cleveland, OH 44106 USA
dc.description.affiliationUniv Utah, Dept Pediat, Salt Lake City, UT USA
dc.description.affiliationAlbert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA
dc.description.affiliationChildrens Hosp Montefiore, Bronx, NY USA
dc.description.affiliationStanford Univ, Dept Pediat, Stanford, CA 94305 USA
dc.description.affiliationHosp Pediat Garrahan, Serv Immunol & Rheumatol, Buenos Aires, DF, Argentina
dc.description.affiliationUniv Fed Sao Paulo, Dept Pediat, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Rio de Janeiro, Rio De Janeiro, Brazil
dc.description.affiliationUniv Toronto, Dept Pediat, Toronto, ON, Canada
dc.description.affiliationUniv Toronto, Dept Pediat, Toronto, ON, Canada
dc.description.affiliationUniv Toronto, Inst Med Sci, Toronto, ON, Canada
dc.description.affiliationUniv Saskatchewan, Dept Pediat, Saskatoon, SK, Canada
dc.description.affiliationUCL, Inst Child Hlth, London, England
dc.description.affiliationUCL, Ctr Paediat & Adolescent Rheumatol, London, England
dc.description.affiliationUniv Barcelona, Hosp Sant Joan Deu, Pediat Rheumatol Unit, Barcelona, Spain
dc.description.affiliationGerman Ctr Pediat & Adolescent Rheumatol, Garmisch Partenkirchen, Germany
dc.description.affiliationUniv Hosp Cal Gustav Carus, Dresden, Germany
dc.description.affiliationCharite, Dept Rheumatol & Clin Immunol, Berlin, Germany
dc.description.affiliationGerman Rheumatism Res Ctr, Epidemiol Unit, Berlin, Germany
dc.description.affiliationRhein Westfal TH Aachen, Dept Pediat, Aachen, Germany
dc.description.affiliationUniv Manchester, Manchester Acad Hlth Sci Ctr, Cent Manchester Univ Hosp NHS Fdn Trust, Natl Inst Hlth Res Manchester Musculoskeletal Bio, Manchester, Lancs, England
dc.description.affiliationUniv Pittsburgh, Dept Med, Pittsburgh, PA USA
dc.description.affiliationUniv Pittsburgh, Dept Human Genet, Pittsburgh, PA USA
dc.description.affiliationCleveland Clin, Dept Gastroenterol & Hepatol, Cleveland, OH 44106 USA
dc.description.affiliationCleveland Clin, Dept Pathobiol, Cleveland, OH 44106 USA
dc.description.affiliationIcahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA
dc.description.affiliationHosp Sick Children, Ctr Appl Gen, Toronto, ON, Canada
dc.description.affiliationPfizer Univ Granada Andalusian Govt, Ctr Genom & Oncol Res, Granada, Spain
dc.description.affiliationKarolinska Inst, Inst Environm Med, Unit Chron Inflammatory Dis, Solna, Sweden
dc.description.affiliationInterdisciplinary Cluster Appl Genoprote Univ Lie, Liege, Belgium
dc.description.affiliationBarcelona Inst Sci & Technol, Ctr Gene Regulat, Barcelona, Spain
dc.description.affiliationUniv Pompeu Fabra UPF, Barcelona, Spain
dc.description.affiliationSidra Med & Res Ctr, Doha, Qatar
dc.description.affiliationIstanbul Univ, Istanbul Fac Med, Istanbul, Turkey
dc.description.affiliationWake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Pediat, Sao Paulo, Brazil
dc.description.provenanceMade available in DSpace on 2020-07-17T14:02:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2017en
dc.description.sourceWeb of Science
dc.description.sponsorshipIntramural Research Programs of the National Institute of Arthritis and Musculoskeletal and Skin Diseases
dc.description.sponsorshipNational Human Genome Research Institute of the National Institutes of Health (NIH)
dc.description.sponsorshipNIH
dc.description.sponsorshipArthritis Research UK
dc.description.sponsorshipGerman Federal Ministry of Education and Research (BMBF)
dc.description.sponsorshipVal A. Browning Charitable Foundation
dc.description.sponsorshipMarcus Foundation
dc.description.sponsorshipProyecto de Excelencia of the Andalousian Government (MA-R)
dc.description.sponsorshipSwedish Association Against Rheumatism (MA-R)
dc.description.sponsorshipWellcome Trust
dc.description.sponsorshipNational Institute for Health Research Biomedical Research Unit Funding Scheme
dc.description.sponsorshipManchester Academic Health Sciences Centre (MAHSC)
dc.description.sponsorshipSPARKS UK
dc.description.sponsorshipMedical Research Council
dc.description.sponsorshipUK National Institute for Health Research GOSH Biomedical Research Centre
dc.description.sponsorshipCanadian Institutes of Health Research
dc.description.sponsorshipArthritis Society (CIHR)
dc.description.sponsorshipCanadian Arthritis Network
dc.description.sponsorshipCincinnati Children's Research Foundation and its Cincinnati Genomic Control Cohort
dc.description.sponsorshipUSA NIH research programme
dc.description.sponsorshipUK Medical Research Council
dc.description.sponsorshipIDIntramural Research Programs of the National Institute of Arthritis and Musculoskeletal and Skin Diseases: Z01-AR041198
dc.description.sponsorshipIDNational Human Genome Research Institute of the National Institutes of Health (NIH): Z01-HG200370
dc.description.sponsorshipIDNIH: R01-AR059049
dc.description.sponsorshipIDNIH: R01AR061297
dc.description.sponsorshipIDNIH: R01-AR060893
dc.description.sponsorshipIDNIH: P30-AR47363
dc.description.sponsorshipIDNIH: P01-AR48929
dc.description.sponsorshipIDNIH: AG030653
dc.description.sponsorshipIDNIH: AG041718
dc.description.sponsorshipIDNIH: AG005133
dc.description.sponsorshipIDNIH: U01-DK062420
dc.description.sponsorshipIDNIH: R01-DK076025
dc.description.sponsorshipIDArthritis Research UK: 20385
dc.description.sponsorshipIDArthritis Research UK: 20542
dc.description.sponsorshipIDGerman Federal Ministry of Education and Research (BMBF): 01ER0813
dc.description.sponsorshipIDProyecto de Excelencia of the Andalousian Government (MA-R): CTS-2548
dc.description.sponsorshipIDWellcome Trust: 098051
dc.description.sponsorshipIDWellcome Trust: 076113/C/04/Z
dc.description.sponsorshipIDWellcome Trust: 068545/Z/02
dc.description.sponsorshipIDSPARKS UK: 08ICH09
dc.description.sponsorshipIDSPARKS UK: 12ICH08
dc.description.sponsorshipIDMedical Research Council: MR/M004600/1
dc.description.sponsorshipIDArthritis Society (CIHR): 82517
dc.description.sponsorshipIDCanadian Arthritis Network: SRI-IJD-01
dc.description.sponsorshipIDUSA NIH research programme: RP-PG-0310-1002
dc.description.sponsorshipIDUK Medical Research Council: G0000934
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1136/annrheumdis-2016-210324
dc.identifier.citationAnnals Of The Rheumatic Diseases. London, v. 76, n. 5, p. -, 2017.
dc.identifier.doi10.1136/annrheumdis-2016-210324
dc.identifier.issn0003-4967
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54703
dc.identifier.wosWOS:000398387200021
dc.language.isoeng
dc.publisherBmj Publishing Group
dc.relation.ispartofAnnals Of The Rheumatic Diseases
dc.rightsAcesso aberto
dc.titleGenetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implicationsen
dc.typeArtigo
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