Sasha Taleban1, Dalin Li2, Stephan R Targan2, Andrew Ippoliti2, Steven R Brant3, Judy H Cho4, Richard H Duerr5, John D Rioux6, Mark S Silverberg7, Eric A Vasiliauskas2, Jerome I Rotter8, Talin Haritunians2, David Q Shih2, Marla Dubinsky9, Gil Y Melmed2, Dermot P B McGovern10. 1. 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. 2. F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 3. Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. 4. Division of Gastroenterology, Mount Sinai Medical Center, New York, NY, USA. 5. Division of Gastroenterology, Hepatology, and Nutrition, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. 6. Department of Medicine, University of Montreal and Montreal Heart Institute, Montreal, QC, Canada. 7. Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. 8. Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics at Harbor-UCLA Medical Center, Torrance, CA, USA. 9. Department of Pediatrics, Division of Gastroenterology, Mount Sinai Medical Center, New York, NY, USA. 10. F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA Dermot.mcgovern@cshs.org.
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.
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.
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