PROJECT SUMMARY/ABSTRACT Crohn?s disease (CD) and ulcerative colitis (UC), also known as the inflammatory bowel diseases (IBD), are characterized by chronic relapsing inflammation of the digestive tract. Although diagnostics and treatments of IBD have improved over the years, patients with IBD still have a much lower quality-of-life than healthy individuals. During the course of this past decade, the medical researchers leading the proposed project, along with their colleagues that make up the NIDDK IBD Genetics Consortium and in collaboration with their international collaborators, have identified 200 regions in the human genome that influence a person?s chances of developing CD or UC ? either increasing or decreasing their chances. Each one of these regions contains zero, one or multiple genes, and hundreds of variations in the genetic code (the genetic code is slightly different from one individual to the next). As part of this project, the researchers will recruit patients and healthy controls, collect biosamples and clinical data that will be part of the NIDDK Central Repositories (in an anonymous fashion to protect participants). The researchers of the proposed project, the NIDDK IBD Genetics Consortium members, and any other qualified researcher will use these samples and data for the discovery of additional risk factors for IBD. The researchers of the proposed project will determine the biological mechanisms by which some these specific changes in the genetic code influence the balance between health and disease (in this case CD or UC), and potentially identify molecules in the blood that can be used as clinical markers of disease, disease subtypes and inflammation status. The objective is to identify the root causes of disease, so that we reveal the key targets for more precise and effective therapies for CD and UC in order to improve the quality of life of patients with CD and UC and eventually lead to the cure of these otherwise lifelong debilitating diseases.