Project description:For most immune-mediated diseases, the main determinant of patient well-being is not the diagnosis itself but instead the course that the disease takes over time (prognosis). Prognosis may vary substantially between patients for reasons that are poorly understood. Familial studies support a genetic contribution to prognosis, but little evidence has been found for a proposed association between prognosis and the burden of susceptibility variants. To better characterize how genetic variation influences disease prognosis, we performed a within-cases genome-wide association study in two cohorts of patients with Crohn's disease. We identified four genome-wide significant loci, none of which showed any association with disease susceptibility. Conversely, the aggregated effect of all 170 disease susceptibility loci was not associated with disease prognosis. Together, these data suggest that the genetic contribution to prognosis in Crohn's disease is largely independent of the contribution to disease susceptibility and point to a biology of prognosis that could provide new therapeutic opportunities.
Project description:Gene expression patterns of Crohn's disease (CD) and ulcerative colitis (UC) colonic specimens were analyzed using whole-genome microarrays. Healthy control samples were included in order to detect gene expression changes associated with CD or UC. CD and UC samples were also compared in order to identify the molecular mechanisms that distinguish both fenotypes of inflammatory bowel disease.
Project description:Gene expression patterns of Crohn's disease (CD) and ulcerative colitis (UC) colonic specimens were analyzed using whole-genome microarrays. Healthy control samples were included in order to detect gene expression changes associated with CD or UC. CD and UC samples were also compared in order to identify the molecular mechanisms that distinguish both fenotypes of inflammatory bowel disease. Total RNA obtained from intestinal biopsies were analyzed using whole-genome microarrays.
Project description:Morphological patterns of Paneth cells are a cellular biomarker in western Crohn’s disease (CD) patients. They integrate genetics and environmental factors, and are associated with outcomes. To broaden the applications of Paneth cell phenotype, identification of novel genetic determinants and clinical validation in other ethnic groups is critical.