University of Miami IBD Genetic Research Center: Understanding the Genetic Architecture of IBD in the South Florida community

University Of Miami School Of Medicine, Coral Gables FL

Investigators

Linked publications, trials & patents

Abstract

PROJECT SUMMARY Inflammatory bowel disease (IBD) is a common and devastating immune-mediated disease in which the mucosal immune system abnormally recognizes the intestinal bacterial flora leading to chronic inflammation. Approximately, 1% of the US population is affected. The causes of Crohn's disease (CD) and ulcerative colitis (UC) lie in the interplay between host response genes and a microbiome with pathogenic properties. IBD incidence has leveled off in the developed world and is rising in the newly industrialized world. In the US, we are witnessing a rising incidence in communities such as South Florida. This provides an opportunity for discovery of disease pathogenesis towards a goal of prevention and improved therapies. Most genetic studies of IBD have not represented the full community of IBD patients and therefore do not represent the totality of the affected population. Our group has used the rising incidence and prevalence of IBD in the South Florida community as a platform to understand the genetic and environmental factors contributing to this shift. We have published highly cited studies of the genotype and phenotype of IBD in the population of South Florida. We have also described inconsistencies in medication usage and surgical rates. Important for the notion that IBD is caused by a gene-environment interaction, we have found that IBD is occurring faster in the last 20 years than in previous generations. We have been very successful in our collection efforts because we have engaged in community outreach and are recognized as regional leaders in the care of IBD patients. We have a unique opportunity and obligation to study this disease within the South Florida population. Many residents of Miami-Dade County trace their ancestors to Europe and Latin America. We are poised to expand our cohort enrollment efforts across Florida. Genome-wide association studies (GWAS) have facilitated the discovery of previously unrecognized genes and pathways in IBD and provided the opportunity for unbiased exploration of the genomes of patients with IBD. We will explore the impact of genomic, transcriptomic, and epigenetic differences in a large cohort of IBD cases to edify how genetics and environment interact to result in distinct phenotypic manifestations of IBD. Our group has expertise and interest in methods to fine-map previously identified risk loci and access the impact of local genetic ancestry on genotype-ancestry interactions in relation to phenotypic characteristics, with the goal of identifying genetic variation of functional significance. Our proposed studies will expand knowledge of disease phenotype and genetic underpinnings in IBD in this growing South Florida cohort in the hopes of developing prevention and improved treatment approaches. The complementary strengths of the two PIs will catapult discoveries in the gene-environment interactions underlying the development of IBD and advance the goals of the IBDGC to enhance understanding of the genetic architecture and pathophysiology of IBD for improved outcomes across the entire US IBD patient population.