Studies of the human genome have revolutionized our ability to identify genes that result in genetic risk for Crohn’s disease and ulcerative colitis. These studies allow scientists to study the mechanisms by which genetic variants influence disease susceptibility, and pave the way for groundbreaking studies to create individualized treatments. Genome-wide association studies in IBD patients have identified 100 non-overlapping genetic markers, of which approximately 50 are unique to either Crohn’s disease or ulcerative colitis.
With such rapid progress in identifying these genetic factors, the challenge for scientists has become understanding just how disease genes and their corresponding alleles are related to health and disease, and finding ways to apply this knowledge to improved patient care through earlier diagnosis, individualized treatment, and identifying those at risk of developing disease to prevent disease altogether.
Like the Microbiome Initiative, the Genetics Initiative will provide a cross-disciplinary and multi-investigator collaborative platform. Its team of investigators will begin by examining existing genome data with the newest sequencing technologies, redefining susceptibility loci into precise genetic mutations in individual genes. The team will leverage genetic discoveries to develop mechanistic understandings of Crohn’s disease and ulcerative colitis and to characterize these diseases at the molecular level. These insights will then be carried forward to develop new approaches to diagnosis and treatment, with the goal of producing practical applications to benefit patients in the clinic.
Ramnik Xavier, M.D., Ph.D., chairman of the department of gastroenterology at Massachusetts General Hospital in Boston, will serve as Principal Investigator (PI) with Herbert “Skip” Virgin, M.D., Ph.D., of Washington University Medical Center in St. Louis as co-PI. The team has identified a steering committee for Phase I of the project, which will assist with the tough choices that will have to be made scientifically and provide an objective assessment of the team’s progress-to-goals. The steering committee will guide the process of choosing and prioritizing genes and pathways, monitor progress and productivity of each of the components, and assist with integration of the components of the initiative.
The overarching goal of this bench-to-bedside initiative is to provide a set of tools that can be used both to guide the development of new treatments for Crohn’s disease and ulcerative colitis, define patient subsets who may respond to specific treatments, and to measure the impact of treatments in patients. In addition to providing crucial insight into IBD, the Genetics Initiative will also expand the scope of knowledge of a wide variety of immune- mediated diseases.