title: Network analysis and juvenile idiopathic arthritis (JIA): a new horizon for the understanding of disease pathogenesis and therapeutic target identification.
abstract: Juvenile idiopathic arthritis (JIA) is a clinically diverse and genetically complex autoimmune disease. Currently, there is very limited understanding of the potential underlying mechanisms that result in the range of phenotypes which constitute JIA.The elucidation of the functional relevance of genetic associations with phenotypic traits is a fundamental problem that hampers the translation of genetic observations to plausible medical interventions. Genome wide association studies, and subsequent fine-mapping studies in JIA patients, have identified many genetic variants associated with disease. Such approaches rely on 'tag' single nucleotide polymorphisms (SNPs). The associated SNPs are rarely functional variants, so the extrapolation of genetic association data to the identification of biologically meaningful findings can be a protracted undertaking. Integrative genomics aims to bridge the gap between genotype and phenotype.Systems biology, principally through network analysis, is emerging as a valuable way to identify biological pathways of relevance to complex genetic diseases. This review aims to highlight recent findings in systems biology related to JIA in an attempt to assist in the understanding of JIA pathogenesis and therapeutic target identification.
authors.affiliation: Musculoskeletal Research Group, The Centre For Musculoskeletal Research, University of Manchester, 2nd Floor, Stopford Building, Oxford Road, Manchester, M13 9PT, UK. rachelle.donn@manchester.ac.uk.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Donn
authors.affiliation: Manchester Academic Health Sciences Centre, Institute for Human Development, Royal Manchester Children's Hospital, 5th Floor Research, Oxford Road, Manchester, M13 9WL, UK.
authors.forename: Chiara
authors.initials: C
authors.lastname: De Leonibus
authors.affiliation: Stem Cell and Leukaemia Proteomics Laboratory, School of Cancer and Imaging Sciences, University of Manchester, Manchester, UK.
authors.forename: Stefan
authors.initials: S
authors.lastname: Meyer
authors.affiliation: Manchester Academic Health Sciences Centre, Institute for Human Development, Royal Manchester Children's Hospital, 5th Floor Research, Oxford Road, Manchester, M13 9WL, UK. adam.stevens@manchester.ac.uk.
authors.forename: Adam
authors.identifier: http://orcid.org/0000-0002-1950-7325
authors.initials: A
authors.lastname: Stevens
mesh_terms: D001171:Arthritis, Juvenile / Q000235:genetics* / Q000378:metabolism; D053263:Gene Regulatory Networks; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D053858:Metabolic Networks and Pathways; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D060066:Protein Interaction Maps; D049490:Systems Biology
keywords: Juvenile idiopathic arthritis; Network analysis; System biology