The Unsolved Link of Genetic Markers and Crohn's Disease Progression: A North American Cohort Experience. Issue 9 (25th February 2019)

• Record Type: Journal Article
• Authors: O'Donnell, Sarah; Borowski, Krzysztof; Espin-Garcia, Osvaldo; Milgrom, Raquel; Kabakchiev, Boyko; Stempak, Joanne; Panikkath, Deepah; Eksteen, Bertus; Xu, Wei; Steinhart, A Hillary; Kaplan, Gilaad G; McGovern, Dermot P B; Silverberg, Mark S
• Is Part Of: Inflammatory bowel diseases. Volume 25:Issue 9(2019)
• Page Start: 1541
• Page End: 1549
• Publication Date: 2019-02-25
• Subjects: Crohn's disease -- genome-wide association -- genetics -- prognosis; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1093/ibd/izz016
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract: Background: While progress has been made in the identification of Crohn's disease (CD) susceptibility loci, efforts to identify a genetic basis for disease progression have been less fruitful. The specific aim of this study was to build upon the major genetic advances made in IBD by applying genome-wide technologies toward predicting disease progression in CD. Methods: Crohn's disease cases (n = 1495) from 3 IBD centers were reviewed by experienced physicians. Clinical and demographic details were collected, focusing on the time to first disease progression. Genome-wide association (GWA) analysis was carried out on 3 clinical outcomes: 1) time to disease progression; 2) time to first abdominal surgery; and 3) a binary analysis of indolent vs progressive disease. Cox-proportional hazard and logistic regression models were used. Results: A GWA analysis was carried out to determine any genetic variation associated with the time to disease progression; 662 cases were included after quality control (QC) and exclusion of any cases with B2/B3 behavior at baseline (n = 450). There were 1360 cases included after QC in the time to abdominal surgery analysis. No variant reached genome-wide significance in any of the 3 analyses performed. Eight known IBD susceptibility single nucleotide polymorphism (SNPs) were found to be associated with time-to-abdominal surgery SMAD3 (rs17293632), CCR6 (rs1819333), CNTF (rs11229555), TSPAN14 (rs7097656), CARD9 (rs10781499), IPMK (rs2790216), IL10 (rs3024505), and SMURF1 (rs9297145) ( P < 0.05). Conclusion: Our GWA study failed to show any SNP-phenotype association reaching genome-wide significance. It is likely that multiple variables affect disease progression, with genetic factors potentially having only a small effect size. Abstract : The purpose of this article is to determine any link between disease progression in Crohn's disease and genetic markers. Identification of markers of disease progression may allow for early inistitution of more aggressive therapy with the aim of altering the natural history of the disease.