This application is submitted in response to RFA DK-06-504 to continue the efforts of the NIDDK Inflammatory Bowel Disease Genetics Consortium (IBDGC) and our role as a Genetic Research Center (GRC). Crohn's disease (CD) and ulcerative colitis (UC) are two common chronic inflammatory diseases of the gastrointestinal tract, collectively known as the inflammatory bowel diseases (IBD). It is estimated that as many as one million Americans are affected with these debilitating diseases. IBD may occur in people of all ages, but it is primarily a disease that arises in adolescents and young adults. Currently there is no known cure for IBD. Over the last five years, a number of IBD genes (CARD15, IBD5, MYO9B, and IL23R) have been identified, but these do not explain all of the genetic risk to IBD. One of the major challenges in complex trait genetics is having sufficiently powered studies. In order to meet this challenge, the NIDDK has supported the creation of the North American IBDGC. This Consortium consists of six GRCs and one data-coordinating center (DCC). The primary goals of this Consortium have been to collect a large and extremely well phenotyped cohort of IBD patients and matched controls and to apply the latest analytical and technological approaches for the discovery of risk factors that influence an individual's predisposition to developing CD or UC. The Universit? de Montr?al GRC (UMGRC) has played and will continue to play an important role in the recruitment of study subjects, collection of samples and information for the NIDDK public IBD repository, and will lead and participate in the studies aimed to: (1) identify genetic risk factors for IBD, (2) understand how these factors can lead to IBD, and (3) determine how this knowledge can improve clinical management of patients with these chronic diseases. IBD is a chronic inflammatory disease of the digestive tract that primarily affects young people and is characterized by long-term illness and the need for potent medical therapy and substantial surgical therapy. Our work will identify IBD genes and is expected to help: (1) identify persons at risk for disease, (2) predict disease course, (3) aid in selection of treatment, (4) understand the biological mechanisms that lead to IBD such that novel preventive and therapeutic interventions can be developed. Advances in IBD gene identification and methodologic approaches may also be applicable to other common genetic disorders.
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