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Title: | Genetic architecture distinguishes systemic juvenile idiopathic arthritis from otherforms of juvenile idiopathic arthritis: clinical and therapeutic implications |
Author: | Ombrello, Michael J. Arthur, Victoria L. Remmers, Elaine F. Hinks, Anne Tachmazidou, Ioanna Grom, Alexei A. Foell, Dirk Martini, Alberto Gattorno, Marco Ozen, Seza Prahalad, Sampath Zeft, Andrew S. Bohnsack, John F. Ilowite, Norman T. Mellins, Elizabeth D. Russo, Ricardo Len, Claudio A. Odete e Hilario, Maria Oliveira, Sheila Yeung, Rae S. M. Rosenberg, Alan M. Wedderburn, Lucy R. Antón López, Jordi Haas, Johannes-Peter Rosen-Wolff, Angela Minden, Kirsten Tenbrock, Klaus Demirkaya, Erkan Cobb, Joanna Baskin, Elizabeth Signa, Sara Shuldiner, Emily Duerr, Richard H. Achkar, Jean-Paul Kamboh, M. Ilyas Kaufman, Kenneth M. Kottyan, Leah C. Pinto, Dalila Scherer, Stephen W. Alarcón Riquelme, Marta Docampo, Elisa Estivill, Xavier, 1955- Gül, Ahmet British Society of Pediatric and Adolescent Rheumatology (BSPAR) Study Group Inception Cohort of Newly Diagnosed Patients with Juvenile Idiopathic Arthritis (ICON-JIA) Study Group Childhood Arthritis Prospective Study (CAPS) Group Randomized Placebo Phase Study of Rilonacept in sJIA (RAPPORT) Investigators Sparks-Childhood Arthritis Response to Medication Study (CHARMS) Group Biologically Based Outcome Predictors in JIA (BBOP) Group Carl D Langefeld Thompson, Susan Zeggini, Eleftheria Kastner, Daniel L. Woo, Patricia Thomson, Wendy |
Keywords: | Artritis Adolescents Genètica humana Arthritis Teenagers Human genetics |
Issue Date: | 7-Dec-2016 |
Publisher: | BMJ Publishing Group |
Abstract: | Objectives Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA. Methods We performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes. Results The major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes. Conclusions The lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways. |
Note: | Reproducció del document publicat a: https://doi.org/10.1136/annrheumdis-2016-210324 |
It is part of: | Annals of the Rheumatic Diseases, 2016, vol. 2016 |
URI: | http://hdl.handle.net/2445/109063 |
Related resource: | https://doi.org/10.1136/annrheumdis-2016-210324 |
ISSN: | 0003-4967 |
Appears in Collections: | Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques) |
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