title: Ocular Manifestations in Inflammatory Bowel Disease Are Associated with Other Extra-intestinal Manifestations, Gender, and Genes Implicated in Other Immune-related Traits.
abstract: BACKGROUND
  There has been considerable progress in identifying inflammatory bowel disease [IBD] susceptibility genes but little progress in examining the role of genetic variation in the development of the extra-intestinal manifestations [EIMs] of IBD. This study identified clinical, serological, and genetic factors associated with ocular EIMs [O-EIMs] in IBD.
  
  
  METHODS
  We performed a retrospective case-control study of IBD patients, comparing those with and without O-EIMs using the Cedars-Sinai IBD Research Repository and the NIDDK IBD Genetics Consortium Repository. Genotyping was performed using Illumina whole genome platforms.
  
  
  RESULTS
  In all, 124 cases and 3328 controls with available clinical data were identified; 103 cases and 2808 controls had genetic data available. Erythema nodosum and peripheral arthritis particularly were common in patients with O-EIMs [p = 2.77 x 10(-13) and p = 2.58 x 10(-13), respectively] with increasing odds ratios for O-EIMs with each additional non-ocular-EIM [for ≥ 2 EIMs, odds ratio 14.72]. Nominal association with O-EIMs was observed at several known IBD susceptibility single nuclear polymorphisms. One locus, containing RBM19, achieved genome-wide level of significance for association with O-EIMs.
  
  
  CONCLUSIONS
  In IBD, O-EIMs co-occur with musculoskeletal and skin manifestations and, in this study, are nominally associated with known IBD loci. Additional cohorts are needed to verify these results and identify additional genes.
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of Arizona College of Medicine, Tucson, AZ, USA F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Sasha
authors.initials: S
authors.lastname: Taleban
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Dalin
authors.initials: D
authors.lastname: Li
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Targan
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Ippoliti
authors.affiliation: Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Brant
authors.affiliation: Division of Gastroenterology, Mount Sinai Medical Center, New York, NY, USA.
authors.forename: Judy H
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Duerr
authors.affiliation: Department of Medicine, University of Montreal and Montreal Heart Institute, Montreal, QC, Canada.
authors.forename: John D
authors.initials: JD
authors.lastname: Rioux
authors.affiliation: Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Silverberg
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Vasiliauskas
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics at Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Talin
authors.initials: T
authors.lastname: Haritunians
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: David Q
authors.initials: DQ
authors.lastname: Shih
authors.affiliation: Department of Pediatrics, Division of Gastroenterology, Mount Sinai Medical Center, New York, NY, USA.
authors.forename: Marla
authors.initials: M
authors.lastname: Dubinsky
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Gil Y
authors.initials: GY
authors.lastname: Melmed
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA Dermot.mcgovern@cshs.org.
authors.forename: Dermot P B
authors.initials: DP
authors.lastname: McGovern
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000704:Analysis of Variance; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D015897:Comorbidity; D003424:Crohn Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D016208:Databases, Factual; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D015994:Incidence; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D017678:Sex Distribution; D014605:Uveitis / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*
keywords: Crohn’s disease; IBD; eye; genetics; ulcerative colitis; uveitis