title: Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis.
abstract: We used the Immunochip array to analyze 2,816 individuals with juvenile idiopathic arthritis (JIA), comprising the most common subtypes (oligoarticular and rheumatoid factor-negative polyarticular JIA), and 13,056 controls. We confirmed association of 3 known JIA risk loci (the human leukocyte antigen (HLA) region, PTPN22 and PTPN2) and identified 14 loci reaching genome-wide significance (P < 5 × 10(-8)) for the first time. Eleven additional new regions showed suggestive evidence of association with JIA (P < 1 × 10(-6)). Dense mapping of loci along with bioinformatics analysis refined the associations to one gene in each of eight regions, highlighting crucial pathways, including the interleukin (IL)-2 pathway, in JIA disease pathogenesis. The entire Immunochip content, the HLA region and the top 27 loci (P < 1 × 10(-6)) explain an estimated 18, 13 and 6% of the risk of JIA, respectively. In summary, this is the largest collection of JIA cases investigated so far and provides new insight into the genetic basis of this childhood autoimmune disease.
authors.affiliation: Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK. anne.hinks@manchester.ac.uk
authors.forename: Anne
authors.initials: A
authors.lastname: Hinks
authors.forename: Joanna
authors.initials: J
authors.lastname: Cobb
authors.forename: Miranda C
authors.initials: MC
authors.lastname: Marion
authors.forename: Sampath
authors.initials: S
authors.lastname: Prahalad
authors.forename: Marc
authors.initials: M
authors.lastname: Sudman
authors.forename: John
authors.initials: J
authors.lastname: Bowes
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
authors.forename: Mary E
authors.initials: ME
authors.lastname: Comeau
authors.forename: Satria
authors.initials: S
authors.lastname: Sajuthi
authors.forename: Robert
authors.initials: R
authors.lastname: Andrews
authors.forename: Milton
authors.initials: M
authors.lastname: Brown
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chen
authors.forename: Patrick
authors.initials: P
authors.lastname: Concannon
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Sarah
authors.initials: S
authors.lastname: Edkins
authors.forename: Stephen
authors.initials: S
authors.lastname: Eyre
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Gaffney
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Guthery
authors.forename: Joel M
authors.initials: JM
authors.lastname: Guthridge
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hunt
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
authors.forename: Mehdi
authors.initials: M
authors.lastname: Keddache
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Moser
authors.forename: Peter A
authors.initials: PA
authors.lastname: Nigrovic
authors.forename: Suna
authors.initials: S
authors.lastname: Onengut-Gumuscu
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Onslow
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Rosé
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Kathryn J A
authors.initials: KJ
authors.lastname: Steel
authors.forename: Edward K
authors.initials: EK
authors.lastname: Wakeland
authors.forename: Carol A
authors.initials: CA
authors.lastname: Wallace
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Wedderburn
authors.forename: Patricia
authors.initials: P
authors.lastname: Woo
authors.forename: John F
authors.initials: JF
authors.lastname: Bohnsack
authors.forename: Johannes Peter
authors.initials: JP
authors.lastname: Haas
authors.forename: David N
authors.initials: DN
authors.lastname: Glass
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Wendy
authors.initials: W
authors.lastname: Thomson
authors.forename: Susan D
authors.initials: SD
authors.lastname: Thompson
mesh_terms: D000328:Adult; D001171:Arthritis, Juvenile / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002874:Chromosome Mapping; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007378:Interleukins / Q000235:genetics; D015810:Linkage Disequilibrium; D058977:Molecular Sequence Annotation; D020641:Polymorphism, Single Nucleotide; D054388:Receptors, CCR / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D012307:Risk Factors
chemical_list: D007378:Interleukins; D054388:Receptors, CCR; D018123:Receptors, Interleukin