HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis
Identifieur interne : 000232 ( Pmc/Corpus ); précédent : 000231; suivant : 000233HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis
Auteurs : Michael J. Ombrello ; Elaine F. Remmers ; Ioanna Tachmazidou ; Alexei Grom ; Dirk Foell ; Johannes-Peter Haas ; Alberto Martini ; Marco Gattorno ; Seza Özen ; Sampath Prahalad ; Andrew S. Zeft ; John F. Bohnsack ; Elizabeth D. Mellins ; Norman T. Ilowite ; Ricardo Russo ; Claudio Len ; Maria Odete E. Hilario ; Sheila Oliveira ; Rae S. M. Yeung ; Alan Rosenberg ; Lucy R. Wedderburn ; Jordi Anton ; Tobias Schwarz ; Anne Hinks ; Yelda Bilginer ; Jane Park ; Joanna Cobb ; Colleen L. Satorius ; Buhm Han ; Elizabeth Baskin ; Sara Signa ; Richard H. Duerr ; J. P. Achkar ; M. Ilyas Kamboh ; Kenneth M. Kaufman ; Leah C. Kottyan ; Dalila Pinto ; Stephen W. Scherer ; Marta E. Alarc N-Riquelme ; Elisa Docampo ; Xavier Estivill ; Ahmet Gül ; Paul I. W. De Bakker ; Soumya Raychaudhuri ; Carl D. Langefeld ; Susan Thompson ; Eleftheria Zeggini ; Wendy Thomson ; Daniel L. Kastner ; Patricia WooSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2015.
Abstract
To determine whether genetic variation within the MHC locus influences the risk of developing systemic juvenile idiopathic arthritis (sJIA), we examined a dense set of MHC region single nucleotide polymorphisms, classic HLA alleles, and the individual amino acids of HLA molecules in nine independent sJIA case-control populations. Association testing revealed that genetic variants within the MHC class II gene cluster significantly influenced sJIA risk in every study population. The strongest risk factor for sJIA was
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DOI: 10.1073/pnas.1520779112
PubMed: 26598658
PubMed Central: 4702958
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>HLA-DRB1*11</italic> and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis</title><author><name sortKey="Ombrello, Michael J" sort="Ombrello, Michael J" uniqKey="Ombrello M" first="Michael J." last="Ombrello">Michael J. Ombrello</name><affiliation><nlm:aff id="aff1">Translational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Remmers, Elaine F" sort="Remmers, Elaine F" uniqKey="Remmers E" first="Elaine F." last="Remmers">Elaine F. Remmers</name><affiliation><nlm:aff id="aff2">Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Tachmazidou, Ioanna" sort="Tachmazidou, Ioanna" uniqKey="Tachmazidou I" first="Ioanna" last="Tachmazidou">Ioanna Tachmazidou</name><affiliation><nlm:aff id="aff3">Human Genetics, The Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Grom, Alexei" sort="Grom, Alexei" uniqKey="Grom A" first="Alexei" last="Grom">Alexei Grom</name><affiliation><nlm:aff id="aff4">Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229;</nlm:aff></affiliation></author><author><name sortKey="Foell, Dirk" sort="Foell, Dirk" uniqKey="Foell D" first="Dirk" last="Foell">Dirk Foell</name><affiliation><nlm:aff id="aff6">Department of Pediatric Rheumatology and Immunology, University Hospital Münster, D-48149 Münster, Germany;</nlm:aff></affiliation></author><author><name sortKey="Haas, Johannes Peter" sort="Haas, Johannes Peter" uniqKey="Haas J" first="Johannes-Peter" last="Haas">Johannes-Peter Haas</name><affiliation><nlm:aff id="aff7">German Center for Pediatric and Adolescent Rheumatology, 82467 Garmisch-Partenkirchen, Germany;</nlm:aff></affiliation></author><author><name sortKey="Martini, Alberto" sort="Martini, Alberto" uniqKey="Martini A" first="Alberto" last="Martini">Alberto Martini</name><affiliation><nlm:aff id="aff8">Department of Pediatrics, University of Genova, 16145 Genoa, Italy;</nlm:aff></affiliation><affiliation><nlm:aff id="aff9">Pediatrics II Unit, G. Gaslini Institute, 16147 Genoa, Italy;</nlm:aff></affiliation></author><author><name sortKey="Gattorno, Marco" sort="Gattorno, Marco" uniqKey="Gattorno M" first="Marco" last="Gattorno">Marco Gattorno</name><affiliation><nlm:aff id="aff9">Pediatrics II Unit, G. Gaslini Institute, 16147 Genoa, Italy;</nlm:aff></affiliation></author><author><name sortKey="Ozen, Seza" sort="Ozen, Seza" uniqKey="Ozen S" first="Seza" last="Özen">Seza Özen</name><affiliation><nlm:aff id="aff10">Department of Pediatric Rheumatology, Hacettepe University, 06100 Ankara, Turkey;</nlm:aff></affiliation></author><author><name sortKey="Prahalad, Sampath" sort="Prahalad, Sampath" uniqKey="Prahalad S" first="Sampath" last="Prahalad">Sampath Prahalad</name><affiliation><nlm:aff id="aff11">Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;</nlm:aff></affiliation><affiliation><nlm:aff id="aff12">Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322;</nlm:aff></affiliation></author><author><name sortKey="Zeft, Andrew S" sort="Zeft, Andrew S" uniqKey="Zeft A" first="Andrew S." last="Zeft">Andrew S. Zeft</name><affiliation><nlm:aff id="aff13">Department of Pediatrics, Cleveland Clinic, Cleveland, OH 44195;</nlm:aff></affiliation></author><author><name sortKey="Bohnsack, John F" sort="Bohnsack, John F" uniqKey="Bohnsack J" first="John F." last="Bohnsack">John F. Bohnsack</name><affiliation><nlm:aff id="aff14">Department of Pediatrics, University of Utah, Salt Lake City, UT 84113;</nlm:aff></affiliation></author><author><name sortKey="Mellins, Elizabeth D" sort="Mellins, Elizabeth D" uniqKey="Mellins E" first="Elizabeth D." last="Mellins">Elizabeth D. Mellins</name><affiliation><nlm:aff id="aff15">Department of Pediatrics, Stanford University, Stanford, CA 94305;</nlm:aff></affiliation></author><author><name sortKey="Ilowite, Norman T" sort="Ilowite, Norman T" uniqKey="Ilowite N" first="Norman T." last="Ilowite">Norman T. Ilowite</name><affiliation><nlm:aff id="aff16">Department of Pediatrics, Albert Einstein College of Medicine and Children’s Hospital at Montefiore, Bronx, NY 10461;</nlm:aff></affiliation></author><author><name sortKey="Russo, Ricardo" sort="Russo, Ricardo" uniqKey="Russo R" first="Ricardo" last="Russo">Ricardo Russo</name><affiliation><nlm:aff id="aff17">Service of Immunology and Rheumatology, Hospital de Pediatria Garrahan, C1245AAM Buenos Aires, Argentina;</nlm:aff></affiliation></author><author><name sortKey="Len, Claudio" sort="Len, Claudio" uniqKey="Len C" first="Claudio" last="Len">Claudio Len</name><affiliation><nlm:aff id="aff18">Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, 04021-001, Brazil;</nlm:aff></affiliation></author><author><name sortKey="Hilario, Maria Odete E" sort="Hilario, Maria Odete E" uniqKey="Hilario M" first="Maria Odete E." last="Hilario">Maria Odete E. Hilario</name><affiliation><nlm:aff id="aff18">Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, 04021-001, Brazil;</nlm:aff></affiliation></author><author><name sortKey="Oliveira, Sheila" sort="Oliveira, Sheila" uniqKey="Oliveira S" first="Sheila" last="Oliveira">Sheila Oliveira</name><affiliation><nlm:aff id="aff19">Universidade Federal de Rio de Janeiro, Rio de Janeiro, 21941-901, Brazil;</nlm:aff></affiliation></author><author><name sortKey="Yeung, Rae S M" sort="Yeung, Rae S M" uniqKey="Yeung R" first="Rae S. M." last="Yeung">Rae S. M. Yeung</name><affiliation><nlm:aff id="aff20">Department of Pediatrics, University of Toronto, Toronto, Canada M5S 1A8;</nlm:aff></affiliation><affiliation><nlm:aff id="aff21">Department of Immunology, University of Toronto, Toronto, Canada M5S 1A8;</nlm:aff></affiliation><affiliation><nlm:aff id="aff22">Institute of Medical Science, University of Toronto, Toronto, Canada M5S 1A8;</nlm:aff></affiliation></author><author><name sortKey="Rosenberg, Alan" sort="Rosenberg, Alan" uniqKey="Rosenberg A" first="Alan" last="Rosenberg">Alan Rosenberg</name><affiliation><nlm:aff id="aff23">Department of Pediatrics, University of Saskatchewan, Saskatoon, Canada S7N 0W8;</nlm:aff></affiliation></author><author><name sortKey="Wedderburn, Lucy R" sort="Wedderburn, Lucy R" uniqKey="Wedderburn L" first="Lucy R." last="Wedderburn">Lucy R. Wedderburn</name><affiliation><nlm:aff id="aff24">Institute of Child Health, University College London, London, WC1N 1EH, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff25">Center of Paediatric and Adolescent Rheumatology, University College London, London, WC1N 1EH, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Anton, Jordi" sort="Anton, Jordi" uniqKey="Anton J" first="Jordi" last="Anton">Jordi Anton</name><affiliation><nlm:aff id="aff26">Pediatric Rheumatology Unit, Hospital Sant Joan de Déu, Universitat de Barcelona, 08950 Barcelona, Spain;</nlm:aff></affiliation></author><author><name sortKey="Schwarz, Tobias" sort="Schwarz, Tobias" uniqKey="Schwarz T" first="Tobias" last="Schwarz">Tobias Schwarz</name><affiliation><nlm:aff id="aff27">Section of Pediatric Rheumatology and Osteology, University of Würzberg, 97080 Würzberg, Germany;</nlm:aff></affiliation></author><author><name sortKey="Hinks, Anne" sort="Hinks, Anne" uniqKey="Hinks A" first="Anne" last="Hinks">Anne Hinks</name><affiliation><nlm:aff id="aff28">Arthritis Research UK Centre for Genetics and Genomics, Manchester Academic Health Centre, University of Manchester, Manchester, M13 9PT, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Bilginer, Yelda" sort="Bilginer, Yelda" uniqKey="Bilginer Y" first="Yelda" last="Bilginer">Yelda Bilginer</name><affiliation><nlm:aff id="aff10">Department of Pediatric Rheumatology, Hacettepe University, 06100 Ankara, Turkey;</nlm:aff></affiliation></author><author><name sortKey="Park, Jane" sort="Park, Jane" uniqKey="Park J" first="Jane" last="Park">Jane Park</name><affiliation><nlm:aff id="aff15">Department of Pediatrics, Stanford University, Stanford, CA 94305;</nlm:aff></affiliation></author><author><name sortKey="Cobb, Joanna" sort="Cobb, Joanna" uniqKey="Cobb J" first="Joanna" last="Cobb">Joanna Cobb</name><affiliation><nlm:aff id="aff28">Arthritis Research UK Centre for Genetics and Genomics, Manchester Academic Health Centre, University of Manchester, Manchester, M13 9PT, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff29">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;</nlm:aff></affiliation></author><author><name sortKey="Satorius, Colleen L" sort="Satorius, Colleen L" uniqKey="Satorius C" first="Colleen L." last="Satorius">Colleen L. Satorius</name><affiliation><nlm:aff id="aff2">Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Han, Buhm" sort="Han, Buhm" uniqKey="Han B" first="Buhm" last="Han">Buhm Han</name><affiliation><nlm:aff id="aff30">Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142;</nlm:aff></affiliation><affiliation><nlm:aff id="aff31">Division of Immunology, Allergy, and Rheumatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115;</nlm:aff></affiliation><affiliation><nlm:aff id="aff32">Department of Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, Republic of Korea;</nlm:aff></affiliation></author><author><name sortKey="Baskin, Elizabeth" sort="Baskin, Elizabeth" uniqKey="Baskin E" first="Elizabeth" last="Baskin">Elizabeth Baskin</name><affiliation><nlm:aff id="aff1">Translational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Signa, Sara" sort="Signa, Sara" uniqKey="Signa S" first="Sara" last="Signa">Sara Signa</name><affiliation><nlm:aff id="aff8">Department of Pediatrics, University of Genova, 16145 Genoa, Italy;</nlm:aff></affiliation></author><author><name sortKey="Duerr, Richard H" sort="Duerr, Richard H" uniqKey="Duerr R" first="Richard H." last="Duerr">Richard H. Duerr</name><affiliation><nlm:aff id="aff33">Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;</nlm:aff></affiliation><affiliation><nlm:aff id="aff34">Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA 15261;</nlm:aff></affiliation></author><author><name sortKey="Achkar, J P" sort="Achkar, J P" uniqKey="Achkar J" first="J. P." last="Achkar">J. P. Achkar</name><affiliation><nlm:aff id="aff35">Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195;</nlm:aff></affiliation><affiliation><nlm:aff id="aff36">Department of Pathobiology, Cleveland Clinic, Cleveland, OH 44195;</nlm:aff></affiliation></author><author><name sortKey="Kamboh, M Ilyas" sort="Kamboh, M Ilyas" uniqKey="Kamboh M" first="M. Ilyas" last="Kamboh">M. Ilyas Kamboh</name><affiliation><nlm:aff id="aff33">Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;</nlm:aff></affiliation></author><author><name sortKey="Kaufman, Kenneth M" sort="Kaufman, Kenneth M" uniqKey="Kaufman K" first="Kenneth M." last="Kaufman">Kenneth M. Kaufman</name><affiliation><nlm:aff id="aff4">Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229;</nlm:aff></affiliation></author><author><name sortKey="Kottyan, Leah C" sort="Kottyan, Leah C" uniqKey="Kottyan L" first="Leah C." last="Kottyan">Leah C. Kottyan</name><affiliation><nlm:aff id="aff4">Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229;</nlm:aff></affiliation></author><author><name sortKey="Pinto, Dalila" sort="Pinto, Dalila" uniqKey="Pinto D" first="Dalila" last="Pinto">Dalila Pinto</name><affiliation><nlm:aff id="aff37">Department of Genetics and Genomic Sciences, Icahn School of Medicine At Mount Sinai, New York, NY 10029;</nlm:aff></affiliation></author><author><name sortKey="Scherer, Stephen W" sort="Scherer, Stephen W" uniqKey="Scherer S" first="Stephen W." last="Scherer">Stephen W. Scherer</name><affiliation><nlm:aff id="aff38">The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada;</nlm:aff></affiliation></author><author><name sortKey="Alarc N Riquelme, Marta E" sort="Alarc N Riquelme, Marta E" uniqKey="Alarc N Riquelme M" first="Marta E." last="Alarc N-Riquelme">Marta E. Alarc N-Riquelme</name><affiliation><nlm:aff id="aff39">Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104;</nlm:aff></affiliation><affiliation><nlm:aff id="aff40">Center for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Government, PTS Granada 18016, Spain;</nlm:aff></affiliation></author><author><name sortKey="Docampo, Elisa" sort="Docampo, Elisa" uniqKey="Docampo E" first="Elisa" last="Docampo">Elisa Docampo</name><affiliation><nlm:aff id="aff41">Interdisciplinary Cluster for Applied Genoproteomics-Université de Liège, 4000-Liège, Belgium;</nlm:aff></affiliation><affiliation><nlm:aff id="aff42">Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, and Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain;</nlm:aff></affiliation></author><author><name sortKey="Estivill, Xavier" sort="Estivill, Xavier" uniqKey="Estivill X" first="Xavier" last="Estivill">Xavier Estivill</name><affiliation><nlm:aff id="aff42">Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, and Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain;</nlm:aff></affiliation></author><author><name sortKey="Gul, Ahmet" sort="Gul, Ahmet" uniqKey="Gul A" first="Ahmet" last="Gül">Ahmet Gül</name><affiliation><nlm:aff id="aff43">Istanbul Faculty of Medicine, Istanbul University, 34390 Istanbul, Turkey;</nlm:aff></affiliation></author><author><name sortKey="De Bakker, Paul I W" sort="De Bakker, Paul I W" uniqKey="De Bakker P" first="Paul I. W." last="De Bakker">Paul I. W. De Bakker</name><affiliation><nlm:aff id="aff44">Department of Epidemiology, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff id="aff45">Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff46">Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Raychaudhuri, Soumya" sort="Raychaudhuri, Soumya" uniqKey="Raychaudhuri S" first="Soumya" last="Raychaudhuri">Soumya Raychaudhuri</name><affiliation><nlm:aff id="aff28">Arthritis Research UK Centre for Genetics and Genomics, Manchester Academic Health Centre, University of Manchester, Manchester, M13 9PT, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff30">Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142;</nlm:aff></affiliation><affiliation><nlm:aff id="aff31">Division of Immunology, Allergy, and Rheumatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115;</nlm:aff></affiliation></author><author><name sortKey="Langefeld, Carl D" sort="Langefeld, Carl D" uniqKey="Langefeld C" first="Carl D." last="Langefeld">Carl D. Langefeld</name><affiliation><nlm:aff id="aff47">Department of Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, NC 27106</nlm:aff></affiliation></author><author><name sortKey="Thompson, Susan" sort="Thompson, Susan" uniqKey="Thompson S" first="Susan" last="Thompson">Susan Thompson</name><affiliation><nlm:aff id="aff4">Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229;</nlm:aff></affiliation></author><author><name sortKey="Zeggini, Eleftheria" sort="Zeggini, Eleftheria" uniqKey="Zeggini E" first="Eleftheria" last="Zeggini">Eleftheria Zeggini</name><affiliation><nlm:aff id="aff3">Human Genetics, The Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Thomson, Wendy" sort="Thomson, Wendy" uniqKey="Thomson W" first="Wendy" last="Thomson">Wendy Thomson</name><affiliation><nlm:aff id="aff28">Arthritis Research UK Centre for Genetics and Genomics, Manchester Academic Health Centre, University of Manchester, Manchester, M13 9PT, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff29">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;</nlm:aff></affiliation></author><author><name sortKey="Kastner, Daniel L" sort="Kastner, Daniel L" uniqKey="Kastner D" first="Daniel L." last="Kastner">Daniel L. Kastner</name><affiliation><nlm:aff id="aff2">Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Woo, Patricia" sort="Woo, Patricia" uniqKey="Woo P" first="Patricia" last="Woo">Patricia Woo</name><affiliation><nlm:aff id="aff25">Center of Paediatric and Adolescent Rheumatology, University College London, London, WC1N 1EH, United Kingdom;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26598658</idno><idno type="pmc">4702958</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702958</idno><idno type="RBID">PMC:4702958</idno><idno type="doi">10.1073/pnas.1520779112</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000232</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000232</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>HLA-DRB1*11</italic> and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis</title><author><name sortKey="Ombrello, Michael J" sort="Ombrello, Michael J" uniqKey="Ombrello M" first="Michael J." last="Ombrello">Michael J. Ombrello</name><affiliation><nlm:aff id="aff1">Translational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Remmers, Elaine F" sort="Remmers, Elaine F" uniqKey="Remmers E" first="Elaine F." last="Remmers">Elaine F. Remmers</name><affiliation><nlm:aff id="aff2">Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Tachmazidou, Ioanna" sort="Tachmazidou, Ioanna" uniqKey="Tachmazidou I" first="Ioanna" last="Tachmazidou">Ioanna Tachmazidou</name><affiliation><nlm:aff id="aff3">Human Genetics, The Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Grom, Alexei" sort="Grom, Alexei" uniqKey="Grom A" first="Alexei" last="Grom">Alexei Grom</name><affiliation><nlm:aff id="aff4">Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229;</nlm:aff></affiliation></author><author><name sortKey="Foell, Dirk" sort="Foell, Dirk" uniqKey="Foell D" first="Dirk" last="Foell">Dirk Foell</name><affiliation><nlm:aff id="aff6">Department of Pediatric Rheumatology and Immunology, University Hospital Münster, D-48149 Münster, Germany;</nlm:aff></affiliation></author><author><name sortKey="Haas, Johannes Peter" sort="Haas, Johannes Peter" uniqKey="Haas J" first="Johannes-Peter" last="Haas">Johannes-Peter Haas</name><affiliation><nlm:aff id="aff7">German Center for Pediatric and Adolescent Rheumatology, 82467 Garmisch-Partenkirchen, Germany;</nlm:aff></affiliation></author><author><name sortKey="Martini, Alberto" sort="Martini, Alberto" uniqKey="Martini A" first="Alberto" last="Martini">Alberto Martini</name><affiliation><nlm:aff id="aff8">Department of Pediatrics, University of Genova, 16145 Genoa, Italy;</nlm:aff></affiliation><affiliation><nlm:aff id="aff9">Pediatrics II Unit, G. Gaslini Institute, 16147 Genoa, Italy;</nlm:aff></affiliation></author><author><name sortKey="Gattorno, Marco" sort="Gattorno, Marco" uniqKey="Gattorno M" first="Marco" last="Gattorno">Marco Gattorno</name><affiliation><nlm:aff id="aff9">Pediatrics II Unit, G. Gaslini Institute, 16147 Genoa, Italy;</nlm:aff></affiliation></author><author><name sortKey="Ozen, Seza" sort="Ozen, Seza" uniqKey="Ozen S" first="Seza" last="Özen">Seza Özen</name><affiliation><nlm:aff id="aff10">Department of Pediatric Rheumatology, Hacettepe University, 06100 Ankara, Turkey;</nlm:aff></affiliation></author><author><name sortKey="Prahalad, Sampath" sort="Prahalad, Sampath" uniqKey="Prahalad S" first="Sampath" last="Prahalad">Sampath Prahalad</name><affiliation><nlm:aff id="aff11">Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;</nlm:aff></affiliation><affiliation><nlm:aff id="aff12">Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322;</nlm:aff></affiliation></author><author><name sortKey="Zeft, Andrew S" sort="Zeft, Andrew S" uniqKey="Zeft A" first="Andrew S." last="Zeft">Andrew S. Zeft</name><affiliation><nlm:aff id="aff13">Department of Pediatrics, Cleveland Clinic, Cleveland, OH 44195;</nlm:aff></affiliation></author><author><name sortKey="Bohnsack, John F" sort="Bohnsack, John F" uniqKey="Bohnsack J" first="John F." last="Bohnsack">John F. Bohnsack</name><affiliation><nlm:aff id="aff14">Department of Pediatrics, University of Utah, Salt Lake City, UT 84113;</nlm:aff></affiliation></author><author><name sortKey="Mellins, Elizabeth D" sort="Mellins, Elizabeth D" uniqKey="Mellins E" first="Elizabeth D." last="Mellins">Elizabeth D. Mellins</name><affiliation><nlm:aff id="aff15">Department of Pediatrics, Stanford University, Stanford, CA 94305;</nlm:aff></affiliation></author><author><name sortKey="Ilowite, Norman T" sort="Ilowite, Norman T" uniqKey="Ilowite N" first="Norman T." last="Ilowite">Norman T. Ilowite</name><affiliation><nlm:aff id="aff16">Department of Pediatrics, Albert Einstein College of Medicine and Children’s Hospital at Montefiore, Bronx, NY 10461;</nlm:aff></affiliation></author><author><name sortKey="Russo, Ricardo" sort="Russo, Ricardo" uniqKey="Russo R" first="Ricardo" last="Russo">Ricardo Russo</name><affiliation><nlm:aff id="aff17">Service of Immunology and Rheumatology, Hospital de Pediatria Garrahan, C1245AAM Buenos Aires, Argentina;</nlm:aff></affiliation></author><author><name sortKey="Len, Claudio" sort="Len, Claudio" uniqKey="Len C" first="Claudio" last="Len">Claudio Len</name><affiliation><nlm:aff id="aff18">Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, 04021-001, Brazil;</nlm:aff></affiliation></author><author><name sortKey="Hilario, Maria Odete E" sort="Hilario, Maria Odete E" uniqKey="Hilario M" first="Maria Odete E." last="Hilario">Maria Odete E. Hilario</name><affiliation><nlm:aff id="aff18">Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, 04021-001, Brazil;</nlm:aff></affiliation></author><author><name sortKey="Oliveira, Sheila" sort="Oliveira, Sheila" uniqKey="Oliveira S" first="Sheila" last="Oliveira">Sheila Oliveira</name><affiliation><nlm:aff id="aff19">Universidade Federal de Rio de Janeiro, Rio de Janeiro, 21941-901, Brazil;</nlm:aff></affiliation></author><author><name sortKey="Yeung, Rae S M" sort="Yeung, Rae S M" uniqKey="Yeung R" first="Rae S. M." last="Yeung">Rae S. M. Yeung</name><affiliation><nlm:aff id="aff20">Department of Pediatrics, University of Toronto, Toronto, Canada M5S 1A8;</nlm:aff></affiliation><affiliation><nlm:aff id="aff21">Department of Immunology, University of Toronto, Toronto, Canada M5S 1A8;</nlm:aff></affiliation><affiliation><nlm:aff id="aff22">Institute of Medical Science, University of Toronto, Toronto, Canada M5S 1A8;</nlm:aff></affiliation></author><author><name sortKey="Rosenberg, Alan" sort="Rosenberg, Alan" uniqKey="Rosenberg A" first="Alan" last="Rosenberg">Alan Rosenberg</name><affiliation><nlm:aff id="aff23">Department of Pediatrics, University of Saskatchewan, Saskatoon, Canada S7N 0W8;</nlm:aff></affiliation></author><author><name sortKey="Wedderburn, Lucy R" sort="Wedderburn, Lucy R" uniqKey="Wedderburn L" first="Lucy R." last="Wedderburn">Lucy R. Wedderburn</name><affiliation><nlm:aff id="aff24">Institute of Child Health, University College London, London, WC1N 1EH, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff25">Center of Paediatric and Adolescent Rheumatology, University College London, London, WC1N 1EH, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Anton, Jordi" sort="Anton, Jordi" uniqKey="Anton J" first="Jordi" last="Anton">Jordi Anton</name><affiliation><nlm:aff id="aff26">Pediatric Rheumatology Unit, Hospital Sant Joan de Déu, Universitat de Barcelona, 08950 Barcelona, Spain;</nlm:aff></affiliation></author><author><name sortKey="Schwarz, Tobias" sort="Schwarz, Tobias" uniqKey="Schwarz T" first="Tobias" last="Schwarz">Tobias Schwarz</name><affiliation><nlm:aff id="aff27">Section of Pediatric Rheumatology and Osteology, University of Würzberg, 97080 Würzberg, Germany;</nlm:aff></affiliation></author><author><name sortKey="Hinks, Anne" sort="Hinks, Anne" uniqKey="Hinks A" first="Anne" last="Hinks">Anne Hinks</name><affiliation><nlm:aff id="aff28">Arthritis Research UK Centre for Genetics and Genomics, Manchester Academic Health Centre, University of Manchester, Manchester, M13 9PT, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Bilginer, Yelda" sort="Bilginer, Yelda" uniqKey="Bilginer Y" first="Yelda" last="Bilginer">Yelda Bilginer</name><affiliation><nlm:aff id="aff10">Department of Pediatric Rheumatology, Hacettepe University, 06100 Ankara, Turkey;</nlm:aff></affiliation></author><author><name sortKey="Park, Jane" sort="Park, Jane" uniqKey="Park J" first="Jane" last="Park">Jane Park</name><affiliation><nlm:aff id="aff15">Department of Pediatrics, Stanford University, Stanford, CA 94305;</nlm:aff></affiliation></author><author><name sortKey="Cobb, Joanna" sort="Cobb, Joanna" uniqKey="Cobb J" first="Joanna" last="Cobb">Joanna Cobb</name><affiliation><nlm:aff id="aff28">Arthritis Research UK Centre for Genetics and Genomics, Manchester Academic Health Centre, University of Manchester, Manchester, M13 9PT, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff29">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;</nlm:aff></affiliation></author><author><name sortKey="Satorius, Colleen L" sort="Satorius, Colleen L" uniqKey="Satorius C" first="Colleen L." last="Satorius">Colleen L. Satorius</name><affiliation><nlm:aff id="aff2">Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Han, Buhm" sort="Han, Buhm" uniqKey="Han B" first="Buhm" last="Han">Buhm Han</name><affiliation><nlm:aff id="aff30">Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142;</nlm:aff></affiliation><affiliation><nlm:aff id="aff31">Division of Immunology, Allergy, and Rheumatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115;</nlm:aff></affiliation><affiliation><nlm:aff id="aff32">Department of Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, Republic of Korea;</nlm:aff></affiliation></author><author><name sortKey="Baskin, Elizabeth" sort="Baskin, Elizabeth" uniqKey="Baskin E" first="Elizabeth" last="Baskin">Elizabeth Baskin</name><affiliation><nlm:aff id="aff1">Translational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Signa, Sara" sort="Signa, Sara" uniqKey="Signa S" first="Sara" last="Signa">Sara Signa</name><affiliation><nlm:aff id="aff8">Department of Pediatrics, University of Genova, 16145 Genoa, Italy;</nlm:aff></affiliation></author><author><name sortKey="Duerr, Richard H" sort="Duerr, Richard H" uniqKey="Duerr R" first="Richard H." last="Duerr">Richard H. Duerr</name><affiliation><nlm:aff id="aff33">Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;</nlm:aff></affiliation><affiliation><nlm:aff id="aff34">Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA 15261;</nlm:aff></affiliation></author><author><name sortKey="Achkar, J P" sort="Achkar, J P" uniqKey="Achkar J" first="J. P." last="Achkar">J. P. Achkar</name><affiliation><nlm:aff id="aff35">Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195;</nlm:aff></affiliation><affiliation><nlm:aff id="aff36">Department of Pathobiology, Cleveland Clinic, Cleveland, OH 44195;</nlm:aff></affiliation></author><author><name sortKey="Kamboh, M Ilyas" sort="Kamboh, M Ilyas" uniqKey="Kamboh M" first="M. Ilyas" last="Kamboh">M. Ilyas Kamboh</name><affiliation><nlm:aff id="aff33">Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;</nlm:aff></affiliation></author><author><name sortKey="Kaufman, Kenneth M" sort="Kaufman, Kenneth M" uniqKey="Kaufman K" first="Kenneth M." last="Kaufman">Kenneth M. Kaufman</name><affiliation><nlm:aff id="aff4">Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229;</nlm:aff></affiliation></author><author><name sortKey="Kottyan, Leah C" sort="Kottyan, Leah C" uniqKey="Kottyan L" first="Leah C." last="Kottyan">Leah C. Kottyan</name><affiliation><nlm:aff id="aff4">Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229;</nlm:aff></affiliation></author><author><name sortKey="Pinto, Dalila" sort="Pinto, Dalila" uniqKey="Pinto D" first="Dalila" last="Pinto">Dalila Pinto</name><affiliation><nlm:aff id="aff37">Department of Genetics and Genomic Sciences, Icahn School of Medicine At Mount Sinai, New York, NY 10029;</nlm:aff></affiliation></author><author><name sortKey="Scherer, Stephen W" sort="Scherer, Stephen W" uniqKey="Scherer S" first="Stephen W." last="Scherer">Stephen W. Scherer</name><affiliation><nlm:aff id="aff38">The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada;</nlm:aff></affiliation></author><author><name sortKey="Alarc N Riquelme, Marta E" sort="Alarc N Riquelme, Marta E" uniqKey="Alarc N Riquelme M" first="Marta E." last="Alarc N-Riquelme">Marta E. Alarc N-Riquelme</name><affiliation><nlm:aff id="aff39">Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104;</nlm:aff></affiliation><affiliation><nlm:aff id="aff40">Center for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Government, PTS Granada 18016, Spain;</nlm:aff></affiliation></author><author><name sortKey="Docampo, Elisa" sort="Docampo, Elisa" uniqKey="Docampo E" first="Elisa" last="Docampo">Elisa Docampo</name><affiliation><nlm:aff id="aff41">Interdisciplinary Cluster for Applied Genoproteomics-Université de Liège, 4000-Liège, Belgium;</nlm:aff></affiliation><affiliation><nlm:aff id="aff42">Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, and Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain;</nlm:aff></affiliation></author><author><name sortKey="Estivill, Xavier" sort="Estivill, Xavier" uniqKey="Estivill X" first="Xavier" last="Estivill">Xavier Estivill</name><affiliation><nlm:aff id="aff42">Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, and Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain;</nlm:aff></affiliation></author><author><name sortKey="Gul, Ahmet" sort="Gul, Ahmet" uniqKey="Gul A" first="Ahmet" last="Gül">Ahmet Gül</name><affiliation><nlm:aff id="aff43">Istanbul Faculty of Medicine, Istanbul University, 34390 Istanbul, Turkey;</nlm:aff></affiliation></author><author><name sortKey="De Bakker, Paul I W" sort="De Bakker, Paul I W" uniqKey="De Bakker P" first="Paul I. W." last="De Bakker">Paul I. W. De Bakker</name><affiliation><nlm:aff id="aff44">Department of Epidemiology, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff id="aff45">Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff46">Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Raychaudhuri, Soumya" sort="Raychaudhuri, Soumya" uniqKey="Raychaudhuri S" first="Soumya" last="Raychaudhuri">Soumya Raychaudhuri</name><affiliation><nlm:aff id="aff28">Arthritis Research UK Centre for Genetics and Genomics, Manchester Academic Health Centre, University of Manchester, Manchester, M13 9PT, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff30">Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142;</nlm:aff></affiliation><affiliation><nlm:aff id="aff31">Division of Immunology, Allergy, and Rheumatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115;</nlm:aff></affiliation></author><author><name sortKey="Langefeld, Carl D" sort="Langefeld, Carl D" uniqKey="Langefeld C" first="Carl D." last="Langefeld">Carl D. Langefeld</name><affiliation><nlm:aff id="aff47">Department of Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, NC 27106</nlm:aff></affiliation></author><author><name sortKey="Thompson, Susan" sort="Thompson, Susan" uniqKey="Thompson S" first="Susan" last="Thompson">Susan Thompson</name><affiliation><nlm:aff id="aff4">Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229;</nlm:aff></affiliation></author><author><name sortKey="Zeggini, Eleftheria" sort="Zeggini, Eleftheria" uniqKey="Zeggini E" first="Eleftheria" last="Zeggini">Eleftheria Zeggini</name><affiliation><nlm:aff id="aff3">Human Genetics, The Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Thomson, Wendy" sort="Thomson, Wendy" uniqKey="Thomson W" first="Wendy" last="Thomson">Wendy Thomson</name><affiliation><nlm:aff id="aff28">Arthritis Research UK Centre for Genetics and Genomics, Manchester Academic Health Centre, University of Manchester, Manchester, M13 9PT, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff29">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;</nlm:aff></affiliation></author><author><name sortKey="Kastner, Daniel L" sort="Kastner, Daniel L" uniqKey="Kastner D" first="Daniel L." last="Kastner">Daniel L. Kastner</name><affiliation><nlm:aff id="aff2">Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Woo, Patricia" sort="Woo, Patricia" uniqKey="Woo P" first="Patricia" last="Woo">Patricia Woo</name><affiliation><nlm:aff id="aff25">Center of Paediatric and Adolescent Rheumatology, University College London, London, WC1N 1EH, United Kingdom;</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>To determine whether genetic variation within the MHC locus influences the risk of developing systemic juvenile idiopathic arthritis (sJIA), we examined a dense set of MHC region single nucleotide polymorphisms, classic HLA alleles, and the individual amino acids of HLA molecules in nine independent sJIA case-control populations. Association testing revealed that genetic variants within the MHC class II gene cluster significantly influenced sJIA risk in every study population. The strongest risk factor for sJIA was <italic>HLA-DRB1*11</italic>, which conferred at least a two-fold increase in disease risk in each population studied. These data implicate the interaction of antigen presenting cells with T cells in the pathogenesis of sJIA.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="iso-abbrev">Proc. Natl. Acad. Sci. U.S.A</journal-id><journal-id journal-id-type="hwp">pnas</journal-id><journal-id journal-id-type="pmc">pnas</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title></journal-title-group><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26598658</article-id><article-id pub-id-type="pmc">4702958</article-id><article-id pub-id-type="publisher-id">201520779</article-id><article-id pub-id-type="doi">10.1073/pnas.1520779112</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Genetics</subject></subj-group></subj-group><series-title>From the Cover</series-title></article-categories><title-group><article-title><italic>HLA-DRB1*11</italic> and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis</article-title><alt-title alt-title-type="short">MHC locus and risk of systemic juvenile arthritis</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ombrello</surname><given-names>Michael J.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Remmers</surname><given-names>Elaine F.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tachmazidou</surname><given-names>Ioanna</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Grom</surname><given-names>Alexei</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Foell</surname><given-names>Dirk</given-names></name><xref ref-type="aff" rid="aff6"><sup>f</sup></xref></contrib><contrib contrib-type="author"><name><surname>Haas</surname><given-names>Johannes-Peter</given-names></name><xref ref-type="aff" rid="aff7"><sup>g</sup></xref></contrib><contrib contrib-type="author"><name><surname>Martini</surname><given-names>Alberto</given-names></name><xref ref-type="aff" rid="aff8"><sup>h</sup></xref><xref ref-type="aff" rid="aff9"><sup>i</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gattorno</surname><given-names>Marco</given-names></name><xref ref-type="aff" rid="aff9"><sup>i</sup></xref></contrib><contrib contrib-type="author"><name><surname>Özen</surname><given-names>Seza</given-names></name><xref ref-type="aff" rid="aff10"><sup>j</sup></xref></contrib><contrib contrib-type="author"><name><surname>Prahalad</surname><given-names>Sampath</given-names></name><xref ref-type="aff" rid="aff11"><sup>k</sup></xref><xref ref-type="aff" rid="aff12"><sup>l</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zeft</surname><given-names>Andrew S.</given-names></name><xref ref-type="aff" rid="aff13"><sup>m</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bohnsack</surname><given-names>John F.</given-names></name><xref ref-type="aff" rid="aff14"><sup>n</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mellins</surname><given-names>Elizabeth D.</given-names></name><xref ref-type="aff" rid="aff15"><sup>o</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ilowite</surname><given-names>Norman T.</given-names></name><xref ref-type="aff" rid="aff16"><sup>p</sup></xref></contrib><contrib contrib-type="author"><name><surname>Russo</surname><given-names>Ricardo</given-names></name><xref ref-type="aff" rid="aff17"><sup>q</sup></xref></contrib><contrib contrib-type="author"><name><surname>Len</surname><given-names>Claudio</given-names></name><xref ref-type="aff" rid="aff18"><sup>r</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hilario</surname><given-names>Maria Odete E.</given-names></name><xref ref-type="aff" rid="aff18"><sup>r</sup></xref></contrib><contrib contrib-type="author"><name><surname>Oliveira</surname><given-names>Sheila</given-names></name><xref ref-type="aff" rid="aff19"><sup>s</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yeung</surname><given-names>Rae S. M.</given-names></name><xref ref-type="aff" rid="aff20"><sup>t</sup></xref><xref ref-type="aff" rid="aff21"><sup>u</sup></xref><xref ref-type="aff" rid="aff22"><sup>v</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rosenberg</surname><given-names>Alan</given-names></name><xref ref-type="aff" rid="aff23"><sup>w</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wedderburn</surname><given-names>Lucy R.</given-names></name><xref ref-type="aff" rid="aff24"><sup>x</sup></xref><xref ref-type="aff" rid="aff25"><sup>y</sup></xref></contrib><contrib contrib-type="author"><name><surname>Anton</surname><given-names>Jordi</given-names></name><xref ref-type="aff" rid="aff26"><sup>z</sup></xref></contrib><contrib contrib-type="author"><name><surname>Schwarz</surname><given-names>Tobias</given-names></name><xref ref-type="aff" rid="aff27"><sup>aa</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hinks</surname><given-names>Anne</given-names></name><xref ref-type="aff" rid="aff28"><sup>bb</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bilginer</surname><given-names>Yelda</given-names></name><xref ref-type="aff" rid="aff10"><sup>j</sup></xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>Jane</given-names></name><xref ref-type="aff" rid="aff15"><sup>o</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cobb</surname><given-names>Joanna</given-names></name><xref ref-type="aff" rid="aff28"><sup>bb</sup></xref><xref ref-type="aff" rid="aff29"><sup>cc</sup></xref></contrib><contrib contrib-type="author"><name><surname>Satorius</surname><given-names>Colleen L.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Han</surname><given-names>Buhm</given-names></name><xref ref-type="aff" rid="aff30"><sup>dd</sup></xref><xref ref-type="aff" rid="aff31"><sup>ee</sup></xref><xref ref-type="aff" rid="aff32"><sup>ff</sup></xref></contrib><contrib contrib-type="author"><name><surname>Baskin</surname><given-names>Elizabeth</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Signa</surname><given-names>Sara</given-names></name><xref ref-type="aff" rid="aff8"><sup>h</sup></xref></contrib><contrib contrib-type="author"><name><surname>Duerr</surname><given-names>Richard H.</given-names></name><xref ref-type="aff" rid="aff33"><sup>gg</sup></xref><xref ref-type="aff" rid="aff34"><sup>hh</sup></xref></contrib><contrib contrib-type="author"><name><surname>Achkar</surname><given-names>J. P.</given-names></name><xref ref-type="aff" rid="aff35"><sup>ii</sup></xref><xref ref-type="aff" rid="aff36"><sup>jj</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kamboh</surname><given-names>M. Ilyas</given-names></name><xref ref-type="aff" rid="aff33"><sup>gg</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kaufman</surname><given-names>Kenneth M.</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kottyan</surname><given-names>Leah C.</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pinto</surname><given-names>Dalila</given-names></name><xref ref-type="aff" rid="aff37"><sup>kk</sup></xref></contrib><contrib contrib-type="author"><name><surname>Scherer</surname><given-names>Stephen W.</given-names></name><xref ref-type="aff" rid="aff38"><sup>ll</sup></xref></contrib><contrib contrib-type="author"><name><surname>Alarcón-Riquelme</surname><given-names>Marta E.</given-names></name><xref ref-type="aff" rid="aff39"><sup>mm</sup></xref><xref ref-type="aff" rid="aff40"><sup>nn</sup></xref></contrib><contrib contrib-type="author"><name><surname>Docampo</surname><given-names>Elisa</given-names></name><xref ref-type="aff" rid="aff41"><sup>oo</sup></xref><xref ref-type="aff" rid="aff42"><sup>pp</sup></xref></contrib><contrib contrib-type="author"><name><surname>Estivill</surname><given-names>Xavier</given-names></name><xref ref-type="aff" rid="aff42"><sup>pp</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gül</surname><given-names>Ahmet</given-names></name><xref ref-type="aff" rid="aff43"><sup>qq</sup></xref></contrib><contrib contrib-type="author"><collab>British Society of Pediatric and Adolescent Rheumatology (BSPAR) Study Group</collab><xref ref-type="fn" rid="fn1"><sup>2</sup></xref></contrib><contrib contrib-type="author"><collab>Childhood Arthritis Prospective Study (CAPS) Group</collab><xref ref-type="fn" rid="fn1"><sup>2</sup></xref></contrib><contrib contrib-type="author"><collab>Randomized Placebo Phase Study of Rilonacept in sJIA (RAPPORT) Investigators</collab><xref ref-type="fn" rid="fn1"><sup>2</sup></xref></contrib><contrib contrib-type="author"><collab>Sparks-Childhood Arthritis Response to Medication Study (CHARMS) Group</collab><xref ref-type="fn" rid="fn1"><sup>2</sup></xref></contrib><contrib contrib-type="author"><collab>Biologically Based Outcome Predictors in JIA (BBOP) Group</collab><xref ref-type="fn" rid="fn1"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>de Bakker</surname><given-names>Paul I. W.</given-names></name><xref ref-type="aff" rid="aff44"><sup>rr</sup></xref><xref ref-type="aff" rid="aff45"><sup>ss</sup></xref><xref ref-type="aff" rid="aff46"><sup>tt</sup></xref></contrib><contrib contrib-type="author"><name><surname>Raychaudhuri</surname><given-names>Soumya</given-names></name><xref ref-type="aff" rid="aff28"><sup>bb</sup></xref><xref ref-type="aff" rid="aff30"><sup>dd</sup></xref><xref ref-type="aff" rid="aff31"><sup>ee</sup></xref></contrib><contrib contrib-type="author"><name><surname>Langefeld</surname><given-names>Carl D.</given-names></name><xref ref-type="aff" rid="aff47"><sup>uu</sup></xref></contrib><contrib contrib-type="author"><name><surname>Thompson</surname><given-names>Susan</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zeggini</surname><given-names>Eleftheria</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Thomson</surname><given-names>Wendy</given-names></name><xref ref-type="aff" rid="aff28"><sup>bb</sup></xref><xref ref-type="aff" rid="aff29"><sup>cc</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kastner</surname><given-names>Daniel L.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Woo</surname><given-names>Patricia</given-names></name><xref ref-type="aff" rid="aff25"><sup>y</sup></xref></contrib><contrib contrib-type="author"><collab>the International Childhood Arthritis Genetics (INCHARGE) Consortium</collab><xref ref-type="fn" rid="fn1"><sup>2</sup></xref></contrib><aff id="aff1"><sup>a</sup>Translational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892;</aff><aff id="aff2"><sup>b</sup>Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;</aff><aff id="aff3"><sup>c</sup>Human Genetics, The Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, United Kingdom;</aff><aff id="aff4"><sup>d</sup>Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229;</aff><aff id="aff5"><sup>e</sup>Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229;</aff><aff id="aff6"><sup>f</sup>Department of Pediatric Rheumatology and Immunology, University Hospital Münster, D-48149 Münster, Germany;</aff><aff id="aff7"><sup>g</sup>German Center for Pediatric and Adolescent Rheumatology, 82467 Garmisch-Partenkirchen, Germany;</aff><aff id="aff8"><sup>h</sup>Department of Pediatrics, University of Genova, 16145 Genoa, Italy;</aff><aff id="aff9"><sup>i</sup>Pediatrics II Unit, G. Gaslini Institute, 16147 Genoa, Italy;</aff><aff id="aff10"><sup>j</sup>Department of Pediatric Rheumatology, Hacettepe University, 06100 Ankara, Turkey;</aff><aff id="aff11"><sup>k</sup>Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;</aff><aff id="aff12"><sup>l</sup>Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322;</aff><aff id="aff13"><sup>m</sup>Department of Pediatrics, Cleveland Clinic, Cleveland, OH 44195;</aff><aff id="aff14"><sup>n</sup>Department of Pediatrics, University of Utah, Salt Lake City, UT 84113;</aff><aff id="aff15"><sup>o</sup>Department of Pediatrics, Stanford University, Stanford, CA 94305;</aff><aff id="aff16"><sup>p</sup>Department of Pediatrics, Albert Einstein College of Medicine and Children’s Hospital at Montefiore, Bronx, NY 10461;</aff><aff id="aff17"><sup>q</sup>Service of Immunology and Rheumatology, Hospital de Pediatria Garrahan, C1245AAM Buenos Aires, Argentina;</aff><aff id="aff18"><sup>r</sup>Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, 04021-001, Brazil;</aff><aff id="aff19"><sup>s</sup>Universidade Federal de Rio de Janeiro, Rio de Janeiro, 21941-901, Brazil;</aff><aff id="aff20"><sup>t</sup>Department of Pediatrics, University of Toronto, Toronto, Canada M5S 1A8;</aff><aff id="aff21"><sup>u</sup>Department of Immunology, University of Toronto, Toronto, Canada M5S 1A8;</aff><aff id="aff22"><sup>v</sup>Institute of Medical Science, University of Toronto, Toronto, Canada M5S 1A8;</aff><aff id="aff23"><sup>w</sup>Department of Pediatrics, University of Saskatchewan, Saskatoon, Canada S7N 0W8;</aff><aff id="aff24"><sup>x</sup>Institute of Child Health, University College London, London, WC1N 1EH, United Kingdom;</aff><aff id="aff25"><sup>y</sup>Center of Paediatric and Adolescent Rheumatology, University College London, London, WC1N 1EH, United Kingdom;</aff><aff id="aff26"><sup>z</sup>Pediatric Rheumatology Unit, Hospital Sant Joan de Déu, Universitat de Barcelona, 08950 Barcelona, Spain;</aff><aff id="aff27"><sup>aa</sup>Section of Pediatric Rheumatology and Osteology, University of Würzberg, 97080 Würzberg, Germany;</aff><aff id="aff28"><sup>bb</sup>Arthritis Research UK Centre for Genetics and Genomics, Manchester Academic Health Centre, University of Manchester, Manchester, M13 9PT, United Kingdom;</aff><aff id="aff29"><sup>cc</sup>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;</aff><aff id="aff30"><sup>dd</sup>Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142;</aff><aff id="aff31"><sup>ee</sup>Division of Immunology, Allergy, and Rheumatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115;</aff><aff id="aff32"><sup>ff</sup>Department of Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, Republic of Korea;</aff><aff id="aff33"><sup>gg</sup>Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;</aff><aff id="aff34"><sup>hh</sup>Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA 15261;</aff><aff id="aff35"><sup>ii</sup>Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195;</aff><aff id="aff36"><sup>jj</sup>Department of Pathobiology, Cleveland Clinic, Cleveland, OH 44195;</aff><aff id="aff37"><sup>kk</sup>Department of Genetics and Genomic Sciences, Icahn School of Medicine At Mount Sinai, New York, NY 10029;</aff><aff id="aff38"><sup>ll</sup>The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada;</aff><aff id="aff39"><sup>mm</sup>Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104;</aff><aff id="aff40"><sup>nn</sup>Center for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Government, PTS Granada 18016, Spain;</aff><aff id="aff41"><sup>oo</sup>Interdisciplinary Cluster for Applied Genoproteomics-Université de Liège, 4000-Liège, Belgium;</aff><aff id="aff42"><sup>pp</sup>Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, and Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain;</aff><aff id="aff43"><sup>qq</sup>Istanbul Faculty of Medicine, Istanbul University, 34390 Istanbul, Turkey;</aff><aff id="aff44"><sup>rr</sup>Department of Epidemiology, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands;</aff><aff id="aff45"><sup>ss</sup>Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands;</aff><aff id="aff46"><sup>tt</sup>Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands; and</aff><aff id="aff47"><sup>uu</sup>Department of Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, NC 27106</aff></contrib-group><contrib-group><contrib contrib-type="collab"><name><surname>Achkar</surname><given-names>J. P.</given-names></name><xref ref-type="aff" rid="aff157"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Alarcón-Riquelme</surname><given-names>Marta E.</given-names></name><xref ref-type="aff" rid="aff158"><sup>2</sup></xref><xref ref-type="aff" rid="aff159"><sup>3</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Allen</surname><given-names>Roger</given-names></name><xref ref-type="aff" rid="aff160"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Anton</surname><given-names>Jordi</given-names></name><xref ref-type="aff" rid="aff161"><sup>5</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Baskin</surname><given-names>Elizabeth</given-names></name><xref ref-type="aff" rid="aff162"><sup>6</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Berg</surname><given-names>Stefan</given-names></name><xref ref-type="aff" rid="aff163"><sup>7</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Bica</surname><given-names>Bianca</given-names></name><xref ref-type="aff" rid="aff164"><sup>8</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Bilginer</surname><given-names>Yelda</given-names></name><xref ref-type="aff" rid="aff165"><sup>9</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Bohnsack</surname><given-names>John F.</given-names></name><xref ref-type="aff" rid="aff166"><sup>10</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Cavalcanti</surname><given-names>Andre</given-names></name><xref ref-type="aff" rid="aff167"><sup>11</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Chaitow</surname><given-names>Jeffrey</given-names></name><xref ref-type="aff" rid="aff48"><sup>12</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Cobb</surname><given-names>Joanna</given-names></name><xref ref-type="aff" rid="aff49"><sup>13</sup></xref><xref ref-type="aff" rid="aff50"><sup>14</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Cuttica</surname><given-names>Rubin</given-names></name><xref ref-type="aff" rid="aff51"><sup>15</sup></xref></contrib><contrib contrib-type="collab"><name><surname>de Bakker</surname><given-names>Paul I. W.</given-names></name><xref ref-type="aff" rid="aff52"><sup>16</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Docampo</surname><given-names>Elisa</given-names></name><xref ref-type="aff" rid="aff53"><sup>17</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Duerr</surname><given-names>Richard</given-names></name><xref ref-type="aff" rid="aff157"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Ellis</surname><given-names>Justine</given-names></name><xref ref-type="aff" rid="aff54"><sup>18</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Estivill</surname><given-names>Xavier</given-names></name><xref ref-type="aff" rid="aff55"><sup>19</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Finkel</surname><given-names>Terri H.</given-names></name><xref ref-type="aff" rid="aff56"><sup>20</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Foell</surname><given-names>Dirk</given-names></name><xref ref-type="aff" rid="aff57"><sup>21</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Gattorno</surname><given-names>Marco</given-names></name><xref ref-type="aff" rid="aff58"><sup>22</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Grom</surname><given-names>Alexei</given-names></name><xref ref-type="aff" rid="aff59"><sup>23</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Gül</surname><given-names>Ahmet</given-names></name><xref ref-type="aff" rid="aff60"><sup>24</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Haas</surname><given-names>Johannes-Peter</given-names></name><xref ref-type="aff" rid="aff61"><sup>25</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Hakonarson</surname><given-names>Hakon</given-names></name><xref ref-type="aff" rid="aff62"><sup>26</sup></xref><xref ref-type="aff" rid="aff63"><sup>27</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Han</surname><given-names>Buhm</given-names></name><xref ref-type="aff" rid="aff64"><sup>28</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Hilario</surname><given-names>Maria Odete E.</given-names></name><xref ref-type="aff" rid="aff65"><sup>29</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Hinks</surname><given-names>Anne</given-names></name><xref ref-type="aff" rid="aff48"><sup>12</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Ilowite</surname><given-names>Norman T.</given-names></name><xref ref-type="aff" rid="aff66"><sup>30</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Kamboh</surname><given-names>M. Ilyas</given-names></name><xref ref-type="aff" rid="aff67"><sup>31</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Kastner</surname><given-names>Daniel L.</given-names></name><xref ref-type="aff" rid="aff68"><sup>32</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Kaufman</surname><given-names>Kenneth</given-names></name><xref ref-type="aff" rid="aff59"><sup>23</sup></xref><xref ref-type="aff" rid="aff69"><sup>33</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Kottyan</surname><given-names>Leah C.</given-names></name><xref ref-type="aff" rid="aff59"><sup>23</sup></xref><xref ref-type="aff" rid="aff69"><sup>33</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Langefeld</surname><given-names>Carl</given-names></name><xref ref-type="aff" rid="aff70"><sup>34</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Len</surname><given-names>Claudio</given-names></name><xref ref-type="aff" rid="aff65"><sup>29</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Martini</surname><given-names>Alberto</given-names></name><xref ref-type="aff" rid="aff58"><sup>22</sup></xref><xref ref-type="aff" rid="aff71"><sup>35</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Mellins</surname><given-names>Elizabeth D.</given-names></name><xref ref-type="aff" rid="aff72"><sup>36</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Minden</surname><given-names>Kirstin</given-names></name><xref ref-type="aff" rid="aff73"><sup>37</sup></xref><xref ref-type="aff" rid="aff74"><sup>38</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Murray</surname><given-names>Kevin</given-names></name><xref ref-type="aff" rid="aff75"><sup>39</sup></xref><xref ref-type="aff" rid="aff76"><sup>40</sup></xref><xref ref-type="aff" rid="aff77"><sup>41</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Oliveira</surname><given-names>Sheila</given-names></name><xref ref-type="aff" rid="aff78"><sup>42</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Ombrello</surname><given-names>Michael J.</given-names></name><xref ref-type="aff" rid="aff162"><sup>6</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Ozen</surname><given-names>Seza</given-names></name><xref ref-type="aff" rid="aff165"><sup>9</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Park</surname><given-names>Jane</given-names></name><xref ref-type="aff" rid="aff72"><sup>36</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Pinto</surname><given-names>Dalila</given-names></name><xref ref-type="aff" rid="aff79"><sup>43</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Prahalad</surname><given-names>Sampath</given-names></name><xref ref-type="aff" rid="aff80"><sup>44</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Quartier</surname><given-names>Pierre</given-names></name><xref ref-type="aff" rid="aff81"><sup>45</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Raychaudhuri</surname><given-names>Soumya</given-names></name><xref ref-type="aff" rid="aff49"><sup>13</sup></xref><xref ref-type="aff" rid="aff64"><sup>28</sup></xref><xref ref-type="aff" rid="aff82"><sup>46</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Remmers</surname><given-names>Elaine F.</given-names></name><xref ref-type="aff" rid="aff68"><sup>32</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Rosenberg</surname><given-names>Alan</given-names></name><xref ref-type="aff" rid="aff83"><sup>47</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Russo</surname><given-names>Ricardo</given-names></name><xref ref-type="aff" rid="aff84"><sup>48</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Satorius</surname><given-names>Colleen</given-names></name><xref ref-type="aff" rid="aff68"><sup>32</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Scherer</surname><given-names>Stephen W.</given-names></name><xref ref-type="aff" rid="aff85"><sup>49</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Schneider</surname><given-names>Rayfel</given-names></name><xref ref-type="aff" rid="aff85"><sup>49</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Schwarz</surname><given-names>Tobias</given-names></name><xref ref-type="aff" rid="aff86"><sup>50</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Singh-Gerwal</surname><given-names>Davinder</given-names></name><xref ref-type="aff" rid="aff86"><sup>50</sup></xref><xref ref-type="aff" rid="aff87"><sup>51</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Tachmazidou</surname><given-names>Ioanna</given-names></name><xref ref-type="aff" rid="aff88"><sup>52</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Thompson</surname><given-names>Susan</given-names></name><xref ref-type="aff" rid="aff59"><sup>23</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Thomson</surname><given-names>Wendy</given-names></name><xref ref-type="aff" rid="aff49"><sup>13</sup></xref><xref ref-type="aff" rid="aff50"><sup>14</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Wedderburn</surname><given-names>Lucy R.</given-names></name><xref ref-type="aff" rid="aff89"><sup>53</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Woo</surname><given-names>Patricia</given-names></name><xref ref-type="aff" rid="aff89"><sup>53</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Wulffraat</surname><given-names>Nico</given-names></name><xref ref-type="aff" rid="aff90"><sup>54</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Yeung</surname><given-names>Rae SM</given-names></name><xref ref-type="aff" rid="aff85"><sup>49</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Zeft</surname><given-names>Andrew S.</given-names></name><xref ref-type="aff" rid="aff67"><sup>31</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Zeggini</surname><given-names>Eleftheria</given-names></name><xref ref-type="aff" rid="aff88"><sup>52</sup></xref></contrib><aff id="aff157"><sup>1</sup>University of Pittsburgh, Pittsburgh,<addr-line>PA</addr-line> 15260;</aff><aff id="aff158"><sup>2</sup>Oklahoma Medical Research Foundation, Oklahoma City,<addr-line>OK</addr-line> 73104;</aff><aff id="aff159"><sup>3</sup>Center for Genomics and Oncological Research (GENYO), Pfizer-University of Granada-Andalusian Government, PTS Granada, 18016,<country>Spain</country>;</aff><aff id="aff160"><sup>4</sup>Royal Children’s Hospital, Melbourne, Victoria,<country>Australia</country>;</aff><aff id="aff161"><sup>5</sup>Hospital Sant Joan de Déu. Universitat de Barcelona, Barcelona,<country>Spain</country>;</aff><aff id="aff162"><sup>6</sup>Translational Genetics and Genomics Unit, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda,<addr-line>MD</addr-line> 20892;</aff><aff id="aff163"><sup>7</sup>Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg,<country>Sweden</country>;</aff><aff id="aff164"><sup>8</sup>Hospital Universitário Clementino Fraga Filho, Rio de Janeiro,<country>Brazil</country>;</aff><aff id="aff165"><sup>9</sup>Hacettepe University, Ankara,<country>Turkey</country></aff><aff id="aff166"><sup>10</sup>University of Utah, Salt Lake City,<addr-line>UT</addr-line> 84112;</aff><aff id="aff167"><sup>11</sup>Universidade Federal de Pernambuco, Recife, PE,<country>Brazil</country>;</aff><aff id="aff48"><sup>12</sup>Children’s Hospital Westmead, Westmead, New South Wales,<country>Australia</country>;</aff><aff id="aff49"><sup>13</sup>Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Institute for Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, Manchester, U.K.;</aff><aff id="aff50"><sup>14</sup>NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHF Foundation Trust, Manchester Academic Health Centre, The University of Manchester, Manchester, U.K.;</aff><aff id="aff51"><sup>15</sup>Hospital General de Niños Pedro de Elizalde, Buenos Aires,<country>Argentina</country>;</aff><aff id="aff52"><sup>16</sup>Department of Epidemiology, Julius Center for Health Sciences and Primary Care and Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht,<country>Netherlands</country>;</aff><aff id="aff53"><sup>17</sup>GIGA-Université de Liège, Liège,<country>Belgium</country>;</aff><aff id="aff54"><sup>18</sup>Genes, Environment & Complex Disease, Murdoch Children’s Research Institute, Parkville, Victoria,<country>Australia</country>;</aff><aff id="aff55"><sup>19</sup>Center for Genomic Regulation, Barcelona,<country>Spain</country>;</aff><aff id="aff56"><sup>20</sup>Department of Pediatrics, Nemours Children's Hospital, Orlando,<addr-line>FL</addr-line> 32827;</aff><aff id="aff57"><sup>21</sup>University Children's Hospital Münster, Münster,<country>Germany</country>;</aff><aff id="aff58"><sup>22</sup>Instituto Giannina Gaslini, Genova,<country>Italy</country>;</aff><aff id="aff59"><sup>23</sup>Cincinnati Children's Hospital Medical Center, Cincinnati,<addr-line>OH</addr-line> 45229;</aff><aff id="aff60"><sup>24</sup>Istanbul Faculty of Medicine, Istanbul University, Istanbul,<country>Turkey</country>;</aff><aff id="aff61"><sup>25</sup>German Center for Pediatric and Adolescent Rheumatology, Gehfeldstrasse 24, 82467 Garmisch-Partenkirchen,<country>Germany</country>;</aff><aff id="aff62"><sup>26</sup>Center for Applied Genomics and Department of Pediatrics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia,PA 19104;</aff><aff id="aff63"><sup>27</sup>Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia,<addr-line>PA</addr-line> 19104;</aff><aff id="aff64"><sup>28</sup>Broad Institute, Cambridge,<addr-line>MA</addr-line> 02142;</aff><aff id="aff65"><sup>29</sup>Universidade Federal de São Paulo/UNIFESP, São Paulo,<country>Brazil</country>;</aff><aff id="aff66"><sup>30</sup>Albert Einstein College of Medicine, Bronx,<addr-line>NY</addr-line> 10461;</aff><aff id="aff67"><sup>31</sup>Cleveland Clinic, Cleveland,<addr-line>OH</addr-line> 44195;</aff><aff id="aff68"><sup>32</sup>Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda,<addr-line>MD</addr-line> 20892;</aff><aff id="aff69"><sup>33</sup>University of Cincinnati, Cincinnati,<addr-line>OH</addr-line> 45220;</aff><aff id="aff70"><sup>34</sup>Wake Forest University Health Sciences, Winston-Salem,<addr-line>NC</addr-line> 27106;</aff><aff id="aff71"><sup>35</sup>University of Genova, Genova,<country>Italy</country>;</aff><aff id="aff72"><sup>36</sup>Stanford University Medical Center, Stanford,<addr-line>CA</addr-line> 94305;</aff><aff id="aff73"><sup>37</sup>German Rheumatism Research Centre Berlin, a Leibniz Institute, Berlin;</aff><aff id="aff74"><sup>38</sup>Children’s University Hospital, Charité University Hospital, Berlin;</aff><aff id="aff75"><sup>39</sup>Rheumatology Department, Princess Margaret Hospital for Children, Perth,<country>Australia</country>;</aff><aff id="aff76"><sup>40</sup>Murdoch Children’s Research Institute, Parkville,<country>Australia</country>;</aff><aff id="aff77"><sup>41</sup>Department of Paediatrics, University of Melbourne, Victoria,<country>Australia</country>;</aff><aff id="aff78"><sup>42</sup>Universidade Federal do Rio de Janeiro, Rio de Janeiro,<country>Brazil</country>;</aff><aff id="aff79"><sup>43</sup>Icahn School of Medicine at Mount Sinai, New York,<addr-line>NY</addr-line> 10029;</aff><aff id="aff80"><sup>44</sup>Emory University School of Medicine, Atlanta,<addr-line>GA</addr-line> 30322;</aff><aff id="aff81"><sup>45</sup>Unité d'Immunologie, Hématologie et Rhumatologie Pediatrique, Université Paris-Descartes, Hôpital Necker-Enfants Malades and Institut IMAGINE, Paris,<country>France</country>;</aff><aff id="aff82"><sup>46</sup>Brigham and Women's Hospital, Harvard Medical School, Boston,<addr-line>MA</addr-line> 02115;</aff><aff id="aff83"><sup>47</sup>University of Saskatchewan, Saskatoon,<country>Canada</country>;</aff><aff id="aff84"><sup>48</sup>Hospital de Pediatria Garrahan, Buenos Aires,<country>Argentina</country>;</aff><aff id="aff85"><sup>49</sup>The Hospital for Sick Children, Toronto,<country>Canada</country>;</aff><aff id="aff86"><sup>50</sup>University of Würzberg, Würzberg,<country>Germany</country>;<sup>50</sup>Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales,<country>Australia</country>;</aff><aff id="aff87"><sup>51</sup>School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales,<country>Australia</country>;</aff><aff id="aff88"><sup>52</sup>The Wellcome Trust Sanger Institute, Hinxton, U.K.;</aff><aff id="aff89"><sup>53</sup>University College London, London, U.K.;</aff><aff id="aff90"><sup>54</sup>Pediatric Immunology, University Medical Center Utrecht, Utrecht,<country>The Netherlands</country>;</aff></contrib-group><contrib-group><contrib contrib-type="collab"><name><surname>Abinum</surname><given-names>Mario</given-names></name><xref ref-type="aff" rid="aff91"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Bell</surname><given-names>A.</given-names></name><xref ref-type="aff" rid="aff92"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Craft</surname><given-names>Alan W.</given-names></name><xref ref-type="aff" rid="aff93"><sup>3</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Crawley</surname><given-names>Esther</given-names></name><xref ref-type="aff" rid="aff94"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>David</surname><given-names>Joel</given-names></name><xref ref-type="aff" rid="aff95"><sup>5</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Foster</surname><given-names>Helen</given-names></name><xref ref-type="aff" rid="aff94"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Gardener-Medwin</surname><given-names>Janet</given-names></name><xref ref-type="aff" rid="aff96"><sup>6</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Griffin</surname><given-names>Jane</given-names></name><xref ref-type="aff" rid="aff97"><sup>7</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Hall</surname><given-names>Ann</given-names></name><xref ref-type="aff" rid="aff98"><sup>8</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Hall</surname><given-names>M.</given-names></name><xref ref-type="aff" rid="aff99"><sup>9</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Herrick</surname><given-names>Ariane L.</given-names></name><xref ref-type="aff" rid="aff100"><sup>10</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Hollingworth</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="aff101"><sup>11</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Holt</surname><given-names>Lennox</given-names></name><xref ref-type="aff" rid="aff102"><sup>12</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Jones</surname><given-names>Stan</given-names></name><xref ref-type="aff" rid="aff103"><sup>13</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Pountain</surname><given-names>Gillian</given-names></name><xref ref-type="aff" rid="aff104"><sup>14</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Ryder</surname><given-names>Clive</given-names></name><xref ref-type="aff" rid="aff105"><sup>15</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Southwood</surname><given-names>Tauny</given-names></name><xref ref-type="aff" rid="aff105"><sup>15</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Stewart</surname><given-names>I.</given-names></name><xref ref-type="aff" rid="aff103"><sup>13</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Venning</surname><given-names>Helen</given-names></name><xref ref-type="aff" rid="aff106"><sup>16</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Wedderburn</surname><given-names>Lucy R.</given-names></name><xref ref-type="aff" rid="aff107"><sup>17</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Woo</surname><given-names>Patricia</given-names></name><xref ref-type="aff" rid="aff94"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Wyatt</surname><given-names>Sue</given-names></name><xref ref-type="aff" rid="aff108"><sup>18</sup></xref></contrib><aff id="aff91"><sup>1</sup>Department of Immunodeficiency and Paediatric Rheumatology, Newcastle University, Newcastle, U.K.;</aff><aff id="aff92"><sup>2</sup>Queens University, Belfast, U.K.;</aff><aff id="aff93"><sup>3</sup>Royal Victoria Infirmary, Newcastle, U.K.;</aff><aff id="aff94"><sup>4</sup>Division of Infection and Immunity, 3rd Floor Rayne Institute, University College London, 5 University St, London, WC1E 6JF, U.K.;</aff><aff id="aff95"><sup>5</sup>Department of Rheumatology, Nuffield Orthopaedic Hospital, Oxford, U.K.;</aff><aff id="aff96"><sup>6</sup>The Royal Hospital for Sick Children, Yorkhill Children's Hospital, Glasgow, U.K.;</aff><aff id="aff97"><sup>7</sup>Chase Farm Hospital, London, U.K.;</aff><aff id="aff98"><sup>8</sup>Department of Rheumatology, Wexham Park Hospital, Berkshire, U.K.;</aff><aff id="aff99"><sup>9</sup>Department of Rheumatology, Cardiff Royal Infirmary, Cardiff, U.K.;</aff><aff id="aff100"><sup>10</sup>University of Manchester, Manchester Academic Health Science Centre, Salford Royal Hospital, Salford, U.K.;</aff><aff id="aff101"><sup>11</sup>Department of Rheumatology, Bristol Royal Infirmary, Bristol, U.K.;</aff><aff id="aff102"><sup>12</sup>Department of Rheumatology, Manchester University, Manchester, U.K.;</aff><aff id="aff103"><sup>13</sup>Victoria Hospital, Blackpool, Lancashire, U.K.;</aff><aff id="aff104"><sup>14</sup>Hitchingbrooke Hospital, Cambridgeshire, U.K.;</aff><aff id="aff105"><sup>15</sup>Department of Paediatric Rheumatology, Institute of Child Health, Birmingham, Children's Hospital-NHS Foundation Trust, University of Birmingham, Whittall Street, Birmingham, U.K.;</aff><aff id="aff106"><sup>16</sup>Nottingham University Hospital, Nottingham, U.K.;</aff><aff id="aff107"><sup>17</sup>Rheumatology Unit, Institute of Child Health, University College London, London, U.K.;</aff><aff id="aff108"><sup>18</sup>Department of Paediatric Rheumatology, Leeds Children Hospital, Leeds, U.K.</aff></contrib-group><contrib-group><contrib contrib-type="collab"><name><surname>Baildam</surname><given-names>Eileen</given-names></name><xref ref-type="aff" rid="aff109"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Bishop</surname><given-names>Nick</given-names></name><xref ref-type="aff" rid="aff110"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Brown</surname><given-names>Lynsey</given-names></name><xref ref-type="aff" rid="aff109"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Buckley</surname><given-names>Joanne</given-names></name><xref ref-type="aff" rid="aff111"><sup>3</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Chieng</surname><given-names>Alice</given-names></name><xref ref-type="aff" rid="aff111"><sup>3</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Carrasco</surname><given-names>Roberto</given-names></name><xref ref-type="aff" rid="aff112"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Cobb</surname><given-names>Joanna</given-names></name><xref ref-type="aff" rid="aff112"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Cook</surname><given-names>Lucy</given-names></name><xref ref-type="aff" rid="aff113"><sup>5</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Davidson</surname><given-names>Joyce</given-names></name><xref ref-type="aff" rid="aff114"><sup>6</sup></xref><xref ref-type="aff" rid="aff115"><sup>7</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Duggan</surname><given-names>Annette</given-names></name><xref ref-type="aff" rid="aff111"><sup>3</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Eltringham</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="aff113"><sup>5</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Foster</surname><given-names>Helen</given-names></name><xref ref-type="aff" rid="aff113"><sup>5</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Friel</surname><given-names>Elizabeth</given-names></name><xref ref-type="aff" rid="aff115"><sup>7</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Friswell</surname><given-names>Mark</given-names></name><xref ref-type="aff" rid="aff113"><sup>5</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Gardner-Medwin</surname><given-names>Janet</given-names></name><xref ref-type="aff" rid="aff115"><sup>7</sup></xref><xref ref-type="aff" rid="aff116"><sup>8</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Gilbert</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="aff112"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Gould</surname><given-names>Vikki</given-names></name><xref ref-type="aff" rid="aff114"><sup>6</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Hadfield</surname><given-names>Kelly</given-names></name><xref ref-type="aff" rid="aff112"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Hyrich</surname><given-names>Kimme</given-names></name><xref ref-type="aff" rid="aff112"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Jones</surname><given-names>Julie</given-names></name><xref ref-type="aff" rid="aff117"><sup>9</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Lal</surname><given-names>Sham</given-names></name><xref ref-type="aff" rid="aff112"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Lay</surname><given-names>Mark</given-names></name><xref ref-type="aff" rid="aff112"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Lloyd</surname><given-names>Gabrielle</given-names></name><xref ref-type="aff" rid="aff109"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Lloyd</surname><given-names>Olivia</given-names></name><xref ref-type="aff" rid="aff109"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Lydon</surname><given-names>Carol</given-names></name><xref ref-type="aff" rid="aff109"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Makengo</surname><given-names>Natasha</given-names></name><xref ref-type="aff" rid="aff117"><sup>9</sup></xref></contrib><contrib contrib-type="collab"><name><surname>McGovern</surname><given-names>Ann</given-names></name><xref ref-type="aff" rid="aff111"><sup>3</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Meijer</surname><given-names>Alexandra</given-names></name><xref ref-type="aff" rid="aff117"><sup>9</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Mills-Wierda</surname><given-names>Nicola</given-names></name><xref ref-type="aff" rid="aff115"><sup>7</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Moorcroft</surname><given-names>Theresa</given-names></name><xref ref-type="aff" rid="aff109"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Price</surname><given-names>Vicki</given-names></name><xref ref-type="aff" rid="aff115"><sup>7</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Qiao</surname><given-names>Liang</given-names></name><xref ref-type="aff" rid="aff113"><sup>5</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Riding</surname><given-names>Kay</given-names></name><xref ref-type="aff" rid="aff114"><sup>6</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Sim</surname><given-names>Jane</given-names></name><xref ref-type="aff" rid="aff115"><sup>7</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Southwood</surname><given-names>Tauny</given-names></name><xref ref-type="aff" rid="aff119"><sup>11</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Thomson</surname><given-names>Wendy</given-names></name><xref ref-type="aff" rid="aff112"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Todd</surname><given-names>Maureen</given-names></name><xref ref-type="aff" rid="aff115"><sup>7</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Tremble</surname><given-names>Susan</given-names></name><xref ref-type="aff" rid="aff109"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Venter</surname><given-names>Katharine</given-names></name><xref ref-type="aff" rid="aff109"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Wade</surname><given-names>Debbie</given-names></name><xref ref-type="aff" rid="aff113"><sup>5</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Ward</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="aff112"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Watson</surname><given-names>Sharon</given-names></name><xref ref-type="aff" rid="aff115"><sup>7</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Webster</surname><given-names>Gwen</given-names></name><xref ref-type="aff" rid="aff109"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Wedderburn</surname><given-names>Lucy R</given-names></name><xref ref-type="aff" rid="aff117"><sup>9</sup></xref><xref ref-type="aff" rid="aff118"><sup>10</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Zelenovic</surname><given-names>Jadranka</given-names></name><xref ref-type="aff" rid="aff115"><sup>7</sup></xref></contrib><aff id="aff109"><sup>1</sup>Alder Hey Children's Hospital, Liverpool, U.K.;</aff><aff id="aff110"><sup>2</sup>Academic Unit of Child Health, University of Sheffield, Sheffield, U.K.;</aff><aff id="aff111"><sup>3</sup>The Royal Manchester Childrens Hospital, Manchester, U.K.;</aff><aff id="aff112"><sup>4</sup>Arthritis Research UK Epidemiology Unit, Stopford Building, Manchester Academic Health Science Centre, NIHR Manchester Musculoskeletal Biomedical Research Unit, The University of Manchester, Manchester, M13 9PT, U.K.;</aff><aff id="aff113"><sup>5</sup>Royal Victoria Infirmary, Newcastle, U.K.;</aff><aff id="aff114"><sup>6</sup>Royal Hospital for Sick Children, Edinburgh, Scotland, U.K.;</aff><aff id="aff115"><sup>7</sup>Royal Hospital for Sick Children, Yorkhill Childrens Hospital, Glasgow, Scotland, U.K.;</aff><aff id="aff116"><sup>8</sup>University of Glasgow, School of Medicine, Glasgow, Scotland, U.K.;</aff><aff id="aff117"><sup>9</sup>Great Ormond Street Hospital, London, U.K.;</aff><aff id="aff118"><sup>10</sup>Rheumatology Unit, UCL Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, U.K.;</aff><aff id="aff119"><sup>11</sup>Department of Paediatric Rheumatology, Institute of Child Health, Birmingham, Children's HospitalNHS Foundation Trust, University of Birmingham, Whittall Street, Birmingham, U.K.</aff></contrib-group><contrib-group><contrib contrib-type="collab"><name><surname>Birmingham</surname><given-names>James D.</given-names></name><xref ref-type="aff" rid="aff120"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Elder</surname><given-names>Melissa</given-names></name><xref ref-type="aff" rid="aff121"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Gottlieb</surname><given-names>Beth S.</given-names></name><xref ref-type="aff" rid="aff122"><sup>3</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Ilowite</surname><given-names>Normal T.</given-names></name><xref ref-type="aff" rid="aff123"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Imundo</surname><given-names>Lisa F.</given-names></name><xref ref-type="aff" rid="aff124"><sup>5</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Kimura</surname><given-names>Yukiko</given-names></name><xref ref-type="aff" rid="aff125"><sup>6</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Lokhnygina</surname><given-names>Yuliya</given-names></name><xref ref-type="aff" rid="aff126"><sup>7</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Miller</surname><given-names>Michael L.</given-names></name><xref ref-type="aff" rid="aff127"><sup>8</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Milojevic</surname><given-names>Diana</given-names></name><xref ref-type="aff" rid="aff128"><sup>9</sup></xref></contrib><contrib contrib-type="collab"><name><surname>O'Neil</surname><given-names>Kathleen</given-names></name><xref ref-type="aff" rid="aff129"><sup>10</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Punaro</surname><given-names>Marilynn G.</given-names></name><xref ref-type="aff" rid="aff130"><sup>11</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Prather</surname><given-names>Kristi</given-names></name><xref ref-type="aff" rid="aff126"><sup>7</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Ruth</surname><given-names>Natasha M.</given-names></name><xref ref-type="aff" rid="aff131"><sup>12</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Sandborg</surname><given-names>Christy I.</given-names></name><xref ref-type="aff" rid="aff132"><sup>13</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Schanberg</surname><given-names>Laura E.</given-names></name><xref ref-type="aff" rid="aff133"><sup>14</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Sherry</surname><given-names>David D.</given-names></name><xref ref-type="aff" rid="aff134"><sup>15</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Singer</surname><given-names>Nora G.</given-names></name><xref ref-type="aff" rid="aff135"><sup>16</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Spalding</surname><given-names>Steven J.</given-names></name><xref ref-type="aff" rid="aff136"><sup>17</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Tarvin</surname><given-names>Stacey E.</given-names></name><xref ref-type="aff" rid="aff129"><sup>10</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Verbsky</surname><given-names>James W.</given-names></name><xref ref-type="aff" rid="aff137"><sup>18</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Wallace</surname><given-names>Carol A.</given-names></name><xref ref-type="aff" rid="aff138"><sup>19</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Zemel</surname><given-names>Lawrence S.</given-names></name><xref ref-type="aff" rid="aff139"><sup>20</sup></xref></contrib><aff id="aff120"><sup>1</sup>Michigan State University College of Human Medicine, East Lansing, MI;</aff><aff id="aff121"><sup>2</sup>University of Florida, Gainesville, FL;</aff><aff id="aff122"><sup>3</sup>Steven and Alexandra Cohen Children's Hospital, New York, NY;</aff><aff id="aff123"><sup>4</sup>Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York</aff><aff id="aff124"><sup>5</sup>Morgan Stanley Children's Hospital of New York-Presbyterian, Columbia University Medical Center, New York, NY;</aff><aff id="aff125"><sup>6</sup>Joseph M. Sanzari Children's Hospital, Hackensack University Medical Center, Hackensack, NJ;</aff><aff id="aff126"><sup>7</sup>Duke Clinical Research Institute, Durham, NC;</aff><aff id="aff127"><sup>8</sup>Ann and Robert H. Lurie Children's Hospital, Chicago, IL;</aff><aff id="aff128"><sup>9</sup>University of California, San Francisco, CA;</aff><aff id="aff129"><sup>10</sup>Riley Hospital for Children,<country>India</country>napolis, IN;</aff><aff id="aff130"><sup>11</sup>Texas Scottish Rite Hospital, Dallas, TX;</aff><aff id="aff131"><sup>12</sup>Medical University of South Carolina, Charleston, SC;</aff><aff id="aff132"><sup>13</sup>Stanford University, Stanford, CA;</aff><aff id="aff133"><sup>14</sup>Duke University Medical Center, Durham, NC;</aff><aff id="aff134"><sup>15</sup>Children's Hospital of Philadelphia, PA;</aff><aff id="aff135"><sup>16</sup>Metro Health Medical Center, Cleveland, OH;</aff><aff id="aff136"><sup>17</sup>The Cleveland Clinic, Cleveland, OH;</aff><aff id="aff137"><sup>18</sup>Medical College of Wisconsin, Milwaukee, WI;</aff><aff id="aff138"><sup>16</sup>Seattle Children's Hospital & Research Institute, Seattle, WA;</aff><aff id="aff139"><sup>20</sup>Connecticut Children's Medical Center, Hartford, CT</aff></contrib-group><contrib-group><contrib contrib-type="collab"><name><surname>Burkle</surname><given-names>Katrin</given-names></name><xref ref-type="aff" rid="aff140"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Cobb</surname><given-names>Joanna</given-names></name><xref ref-type="aff" rid="aff141"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Etheridge</surname><given-names>Angela</given-names></name><xref ref-type="aff" rid="aff142"><sup>3</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Gilbert</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="aff141"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Hinks</surname><given-names>Anne</given-names></name><xref ref-type="aff" rid="aff141"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Hirani</surname><given-names>Shashi</given-names></name><xref ref-type="aff" rid="aff140"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Kassoumeri</surname><given-names>Laura</given-names></name><xref ref-type="aff" rid="aff142"><sup>3</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Lal</surname><given-names>Sham</given-names></name><xref ref-type="aff" rid="aff141"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Melville</surname><given-names>Laura</given-names></name><xref ref-type="aff" rid="aff140"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Moncrieffe</surname><given-names>Halima</given-names></name><xref ref-type="aff" rid="aff142"><sup>3</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Mulligan</surname><given-names>Kathleen</given-names></name><xref ref-type="aff" rid="aff140"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Newman</surname><given-names>Stanton</given-names></name><xref ref-type="aff" rid="aff140"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Patrick</surname><given-names>Fiona</given-names></name><xref ref-type="aff" rid="aff142"><sup>3</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Southwood</surname><given-names>Tauny</given-names></name><xref ref-type="aff" rid="aff143"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Thomson</surname><given-names>Wendy</given-names></name><xref ref-type="aff" rid="aff141"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Ursu</surname><given-names>Simona</given-names></name><xref ref-type="aff" rid="aff142"><sup>3</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Wedderburn</surname><given-names>Lucy R</given-names></name><xref ref-type="aff" rid="aff142"><sup>3</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Whitworth</surname><given-names>Pamela</given-names></name><xref ref-type="aff" rid="aff143"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Woo</surname><given-names>Patricia</given-names></name><xref ref-type="aff" rid="aff144"><sup>5</sup></xref></contrib><aff id="aff140"><sup>1</sup>Health Psychology, School of Health Sciences, City University, 20 Bartholomew Close, London, U.K.;</aff><aff id="aff141"><sup>2</sup>Arthritis Research UK Epidemiology Unit, Stopford Building, Manchester Academic Health Science Centre, NIHR Manchester Musculoskeletal Biomedical Research Unit, The University of Manchester, Manchester, M13 9PT, U.K.;</aff><aff id="aff142"><sup>3</sup>Rheumatology Unit, Institute of Child Health, University College London, London, U.K.;</aff><aff id="aff143"><sup>4</sup>Department of Paediatric Rheumatology, Institute of Child Health, Birmingham, Children's Hospital-NHS Foundation Trust, University of Birmingham, Whittall Street, Birmingham, U.K.;</aff><aff id="aff144"><sup>5</sup>Division of Infection and Immunity, 3rd Floor Rayne Institute, University College London, 5 University St, London, WC1E 6JF, U.K.</aff></contrib-group><contrib-group><contrib contrib-type="collab"><name><surname>Baxter-Jones</surname><given-names>Adam</given-names></name><xref ref-type="aff" rid="aff145"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Benseler</surname><given-names>Susanne</given-names></name><xref ref-type="aff" rid="aff146"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Boire</surname><given-names>Gilles</given-names></name><xref ref-type="aff" rid="aff147"><sup>3</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Cabral</surname><given-names>David A.</given-names></name><xref ref-type="aff" rid="aff148"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Cameron</surname><given-names>Bonnie</given-names></name><xref ref-type="aff" rid="aff146"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Campillo</surname><given-names>Sarah</given-names></name><xref ref-type="aff" rid="aff149"><sup>5</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Chedeville</surname><given-names>Gaëlle</given-names></name><xref ref-type="aff" rid="aff149"><sup>5</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Chetaille</surname><given-names>Anne-Laure</given-names></name><xref ref-type="aff" rid="aff150"><sup>6</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Dancey</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="aff151"><sup>7</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Duffy</surname><given-names>Ciaran</given-names></name><xref ref-type="aff" rid="aff152"><sup>8</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Duffy</surname><given-names>Karen Watanabe</given-names></name><xref ref-type="aff" rid="aff152"><sup>8</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Ellsworth</surname><given-names>Janet</given-names></name><xref ref-type="aff" rid="aff153"><sup>9</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Feldman</surname><given-names>Brian</given-names></name><xref ref-type="aff" rid="aff146"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Gibbon</surname><given-names>Michele</given-names></name><xref ref-type="aff" rid="aff152"><sup>8</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Guillet</surname><given-names>Chantal</given-names></name><xref ref-type="aff" rid="aff154"><sup>10</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Guzman</surname><given-names>Jaime</given-names></name><xref ref-type="aff" rid="aff148"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Houghton</surname><given-names>Kristin</given-names></name><xref ref-type="aff" rid="aff148"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Huber</surname><given-names>Adam</given-names></name><xref ref-type="aff" rid="aff155"><sup>11</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Jurencak</surname><given-names>Roman</given-names></name><xref ref-type="aff" rid="aff152"><sup>8</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Lang</surname><given-names>Bianca</given-names></name><xref ref-type="aff" rid="aff155"><sup>11</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Laxer</surname><given-names>Ronald</given-names></name><xref ref-type="aff" rid="aff146"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Maenz</surname><given-names>Lynn</given-names></name><xref ref-type="aff" rid="aff145"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Matheson</surname><given-names>Loren</given-names></name><xref ref-type="aff" rid="aff145"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Oen</surname><given-names>Kiem</given-names></name><xref ref-type="aff" rid="aff156"><sup>12</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Petty</surname><given-names>Ross</given-names></name><xref ref-type="aff" rid="aff148"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Ramsey</surname><given-names>Suzanne</given-names></name><xref ref-type="aff" rid="aff155"><sup>11</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Rezaei</surname><given-names>Elham</given-names></name><xref ref-type="aff" rid="aff145"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Rosenberg</surname><given-names>Alan</given-names></name><xref ref-type="aff" rid="aff145"><sup>1</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Roth</surname><given-names>Johannes</given-names></name><xref ref-type="aff" rid="aff152"><sup>8</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Schneider</surname><given-names>Rayfel</given-names></name><xref ref-type="aff" rid="aff146"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Scuccimarri</surname><given-names>Rosie</given-names></name><xref ref-type="aff" rid="aff149"><sup>5</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Silverman</surname><given-names>Earl</given-names></name><xref ref-type="aff" rid="aff146"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Spiegel</surname><given-names>Lynn</given-names></name><xref ref-type="aff" rid="aff146"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Stringer</surname><given-names>Elizabeth</given-names></name><xref ref-type="aff" rid="aff155"><sup>11</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Tse</surname><given-names>Shirley</given-names></name><xref ref-type="aff" rid="aff146"><sup>2</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Tucker</surname><given-names>Lori B.</given-names></name><xref ref-type="aff" rid="aff148"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Turvey</surname><given-names>Stuart</given-names></name><xref ref-type="aff" rid="aff148"><sup>4</sup></xref></contrib><contrib contrib-type="collab"><name><surname>Yeung</surname><given-names>Rae SM</given-names></name><xref ref-type="aff" rid="aff146"><sup>2</sup></xref></contrib><aff id="aff145"><sup>1</sup>University of Saskatchewan, Saskatoon,<country>Canada</country>;</aff><aff id="aff146"><sup>2</sup>Hospital for Sick Children, Toronto,<country>Canada</country>;</aff><aff id="aff147"><sup>3</sup>l’Université de Sherbrooke, Quebec,<country>Canada</country>;</aff><aff id="aff148"><sup>4</sup>British Columbia Children’s Hospital, Vancouver,<country>Canada</country>;</aff><aff id="aff149"><sup>5</sup>McGill University, Montreal, Quebec,<country>Canada</country>;</aff><aff id="aff150"><sup>6</sup>le Centre Hospitalier Universitaire de Quebec, Quebec,<country>Canada</country>;</aff><aff id="aff151"><sup>7</sup>Janeway Children’s Hospital and Rehabilitation Centre, St.John’s, Newfoundland and Labrador,<country>Canada</country>;</aff><aff id="aff152"><sup>8</sup>Children<sup>1</sup>s Hospital of Eastern Ontario, Ottawa,<country>Canada</country>;</aff><aff id="aff153"><sup>9</sup>University of Alberta, Edmonton,<country>Canada</country>;</aff><aff id="aff154"><sup>10</sup>Sante et Services Sociaux, Quebec,<country>Canada</country>;</aff><aff id="aff155"><sup>11</sup>IWK Health Centre, Halifax, NS,<country>Canada</country>;</aff><aff id="aff156"><sup>12</sup>University of Manitoba, Winnipeg,<country>Canada</country></aff></contrib-group><author-notes><corresp id="cor1"><sup>1</sup>To whom correspondence may be addressed. Email: <email>ombrellomj@mail.nih.gov</email> or <email>kastnerd@mail.nih.gov</email>.</corresp><fn fn-type="edited-by"><p>Contributed by Daniel L. Kastner, October 21, 2015 (sent for review June 8, 2015; reviewed by Jos van der Meer and Shumpei Yokota)</p></fn><fn fn-type="con"><p>Author contributions: M.J.O., E.F.R., I.T., A. Grom, D.F., J.-P.H., A.M., M.G., S.Ö., S.P., A.S.Z., J.F.B., E.D.M., N.T.I., R.R., C.L., M.O.E.H., S.O., R.S.M.Y., A.R., L.R.W., J.A., T.S., A.H., Y.B., J.P., J.C., C.L.S., E.B., R.H.D., J.P.A., M.I.K., K.M.K., L.C.K., D.P., S.W.S., M.E.A.-R., E.D., X.E., A. Gül, BSPAR, CAPS, RAPPORT, CHARMS, BBOP, C.D.L., E.Z., W.T., D.L.K., P.W., and INCHARGE designed research; M.J.O., E.F.R., I.T., A. Grom, D.F., J.-P.H., A.M., M.G., S.Ö, S.P., A.S.Z., J.F.B., E.D.M., N.T.I., R.R., C.L., M.O.E.H., S.O., R.S.M.Y., A.R., L.R.W., J.A., T.S., Y.B., C.L.S., E.B., S.S., E.Z., W.T., D.L.K., and P.W. performed research; B.H., P.I.W.d.B., and S.R. contributed new reagents/analytic tools; M.J.O., E.F.R., I.T., A. Grom, A.M., M.G., S.Ö., E.D.M., R.S.M.Y., C.D.L., S.T., E.Z., W.T., D.L.K., and P.W. analyzed data; and M.J.O., E.F.R., A. Grom, M.G., S.Ö., J.F.B., E.D.M., R.R., R.S.M.Y., L.R.W., S.T., E.Z., W.T., D.L.K., and P.W. wrote the paper.</p></fn><fn fn-type="con"><p>Reviewers: J.v.d.M., Radboud University Nijmegen Medical Centre; and S.Y., Yokohama City University.</p></fn></author-notes><pub-date pub-type="ppub"><day>29</day><month>12</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>23</day><month>11</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>23</day><month>11</month><year>2015</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>112</volume><issue>52</issue><fpage>15970</fpage><lpage>15975</lpage><permissions><license license-type="open-access"><license-p>Freely available online through the PNAS open access option.</license-p></license></permissions><self-uri xlink:title="pdf" xlink:href="pnas.201520779.pdf"></self-uri><abstract abstract-type="executive-summary"><title>Significance</title><p>To determine whether genetic variation within the MHC locus influences the risk of developing systemic juvenile idiopathic arthritis (sJIA), we examined a dense set of MHC region single nucleotide polymorphisms, classic HLA alleles, and the individual amino acids of HLA molecules in nine independent sJIA case-control populations. Association testing revealed that genetic variants within the MHC class II gene cluster significantly influenced sJIA risk in every study population. The strongest risk factor for sJIA was <italic>HLA-DRB1*11</italic>, which conferred at least a two-fold increase in disease risk in each population studied. These data implicate the interaction of antigen presenting cells with T cells in the pathogenesis of sJIA.</p></abstract><abstract><p>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 [<italic>P</italic> = 2.8 × 10<sup>−17</sup>, 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 [<italic>P</italic> = 1.0 × 10<sup>−5</sup>, 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 <italic>HLA-DRB1*11</italic> and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [<italic>P</italic> = 2.7 × 10<sup>−16</sup>, OR 2.3 (1.9, 2.8)], as was the <italic>HLA-DRB1*11—HLA-DQA1*05—HLA-DQB1*03</italic> haplotype [6.4 × 10<sup>−17</sup>, 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.</p></abstract><kwd-group><kwd>systemic juvenile idiopathic arthritis</kwd><kwd>Still’s disease</kwd><kwd>human leukocyte antigen</kwd><kwd>autoinflammation</kwd></kwd-group><funding-group><award-group id="gs1"><funding-source id="sp1">HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)<named-content content-type="funder-id">100000069</named-content></funding-source><award-id rid="sp1">Z01-AR041198</award-id></award-group><award-group id="gs2"><funding-source id="sp2">HHS | NIH | National Human Genome Research Institute (NHGRI)<named-content content-type="funder-id">100000051</named-content></funding-source><award-id rid="sp2">Z01-HG200370</award-id></award-group><award-group id="gs3"><funding-source id="sp3">HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)<named-content content-type="funder-id">100000069</named-content></funding-source><award-id rid="sp3">R01-AR059049</award-id></award-group><award-group id="gs4"><funding-source id="sp4">HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)<named-content content-type="funder-id">100000069</named-content></funding-source><award-id rid="sp4">R01-AR060893</award-id></award-group><award-group id="gs5"><funding-source id="sp5">HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)<named-content content-type="funder-id">100000069</named-content></funding-source><award-id rid="sp5">N1R01-AR062886</award-id></award-group><award-group id="gs6"><funding-source id="sp6">Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)<named-content content-type="funder-id">501100003246</named-content></funding-source><award-id rid="sp6">016.126.354</award-id></award-group><award-group id="gs7"><funding-source id="sp7">Wellcome Trust<named-content content-type="funder-id">100004440</named-content></funding-source><award-id rid="sp7">098051</award-id></award-group><award-group id="gs8"><funding-source id="sp8">Sparks<named-content content-type="funder-id">501100000861</named-content></funding-source><award-id rid="sp8">08ICH09 and 12ICH08</award-id></award-group><award-group id="gs9"><funding-source id="sp9">Medical Research Council (MRC)<named-content content-type="funder-id">501100000265</named-content></funding-source><award-id rid="sp9">MR/M004600/1</award-id></award-group></funding-group><counts><page-count count="6"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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