I think it fair to state that elucidating the pathogenesis of inflammatory bowel disease (IBD--ulcerative colitis and Crohn's disease) has been a decades-long exercise in futility. But recently published and presented genome-wide association studies (GWAS) in (IBD) have advanced the understanding of the pathogenesis of IBD. The International IBD Genetics Consortium presented 2 key studies at the recent Digestive Diseases Week 2010 conference.
One of these studies was presented in the "Immunology, Microbiology, and Inflammatory Bowel Disease Distinguished Abstract Plenary" session by the Consortium authored by Parkes et al (abstract) was an multinational GWAS of CD in patients of European descent that identified 18 new susceptibility loci associated with CD that includes candidate genes such as NOTCH1, SMAD3, ICAM3/ICAM5, and MUC1.
A similarly designed study of UC involving N.American and European patients was presented in the "Clinical Practice Distinguished Abstract Plenary" session by John Rioux of the IBD Genetics Consortium (abstract). This study identified 75 independent susceptibility loci associated with UC, including all previously identified susceptibility loci and 20 new loci that appear to be UC-specfic. Interestingly, about half of the 75 loci have previously been associated with CD and of the ~45 putative novel loci, 25 have previously been associated with other autoimmune chronic inflammatory diseases. These results strongly support the hypothesis that certain biological pathways are common between inflammatory diseases. Although the Consortium currently testing all novel loci in an independent group of UC patients, preliminary results provide convincing evidence of association to genes with likely biological significance to disease pathogenesis, including TNFRSF14, JAK2, and CARD9.
This is some very interesting data that not only demonstrate the power of GWAS but also are first steps in identifying markers for IBD and molecular pathways in the pathogenesis of IBD that could be exploited in developing pharmacological targets.
Members of the Consortium recently published a review of UC susceptibility loci in Nature Genetics 2010;42:332-337.