title: Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis.
abstract: OBJECTIVE
  To use high-density genotyping to investigate the genetic associations of acute anterior uveitis (AAU) in patients with and those without ankylosing spondylitis (AS).
  
  
  METHODS
  We genotyped samples from 1,711 patients with AAU (either primary or combined with AS), 2,339 AS patients without AAU, and 10,000 control subjects on an Illumina Immunochip Infinium microarray. We also used data for AS patients from previous genome-wide association studies to investigate the AS risk locus ANTXR2 for its putative effect in AAU. ANTXR2 expression in mouse eyes was investigated by real-time quantitative reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  A comparison between all patients with AAU and healthy control subjects showed strong association over HLA-B, corresponding to the HLA-B27 tag single-nucleotide polymorphism rs116488202. The association of 3 non-major histocompatibility complex loci, IL23R, the intergenic region 2p15, and ERAP1, reached genome-wide significance (P < 5 × 10(-8)). Five loci harboring the immune-related genes IL10-IL19, IL18R1-IL1R1, IL6R, the chromosome 1q32 locus harboring KIF21B, as well as the eye-related gene EYS, were also associated, reaching a suggestive level of significance (P < 5 × 10(-6)). Several previously confirmed AS associations demonstrated significant differences in effect size between AS patients with AAU and AS patients without AAU. ANTXR2 expression varied across eye compartments.
  
  
  CONCLUSIONS
  These findings of both novel AAU-specific associations and associations shared with AS demonstrate overlapping but also distinct genetic susceptibility loci for AAU and AS. The associations in IL10 and IL18R1 are shared with inflammatory bowel disease, suggesting common etiologic pathways.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Robinson
authors.forename: Theodora A M
authors.initials: TA
authors.lastname: Claushuis
authors.forename: Adrian
authors.initials: A
authors.lastname: Cortes
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Martin
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.forename: Paul
authors.initials: P
authors.lastname: Leo
authors.forename: Pamela
authors.initials: P
authors.lastname: Mukhopadhyay
authors.forename: Linda A
authors.initials: LA
authors.lastname: Bradbury
authors.forename: Katie
authors.initials: K
authors.lastname: Cremin
authors.forename: Jessica
authors.initials: J
authors.lastname: Harris
authors.forename: Walter P
authors.initials: WP
authors.lastname: Maksymowych
authors.forename: Robert D
authors.initials: RD
authors.lastname: Inman
authors.forename: Proton
authors.initials: P
authors.lastname: Rahman
authors.forename: Nigil
authors.initials: N
authors.lastname: Haroon
authors.forename: Lianne
authors.initials: L
authors.lastname: Gensler
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Powell
authors.forename: Irene E
authors.initials: IE
authors.lastname: van der Horst-Bruinsma
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
authors.forename: Lyndell L
authors.initials: LL
authors.lastname: Lim
authors.forename: Denis
authors.initials: D
authors.lastname: Wakefield
authors.forename: Peter
authors.initials: P
authors.lastname: McCluskey
authors.forename: Valentina
authors.initials: V
authors.lastname: Voigt
authors.forename: Peter
authors.initials: P
authors.lastname: Fleming
authors.forename: Mariapia
authors.initials: M
authors.lastname: Degli-Esposti
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Pointon
authors.forename: Michael H
authors.initials: MH
authors.lastname: Weisman
authors.forename: B Paul
authors.initials: BP
authors.lastname: Wordsworth
authors.forename: John D
authors.initials: JD
authors.lastname: Reveille
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
mesh_terms: D000626:Aminopeptidases / Q000235:genetics; D016022:Case-Control Studies; D055106:Genome-Wide Association Study; D005838:Genotype; D015796:HLA-B27 Antigen / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D053727:Interleukin-18 Receptor alpha Subunit / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D018123:Receptors, Interleukin / Q000235:genetics; D018000:Receptors, Peptide / Q000235:genetics; D013167:Spondylitis, Ankylosing / Q000235:genetics*; D014606:Uveitis, Anterior / Q000235:genetics*
chemical_list: C447150:ANTXR2 protein, human; D015796:HLA-B27 Antigen; C508572:IL18R1 protein, human; C515500:IL23R protein, human; D053727:Interleukin-18 Receptor alpha Subunit; D015778:Minor Histocompatibility Antigens; D018123:Receptors, Interleukin; D018000:Receptors, Peptide; D016753:Interleukin-10; D000626:Aminopeptidases; C464841:ERAP1 protein, human