Inflammatory bowel disease (IBD) is a group of inflammatory conditions in the colon and small intestine. Crohn's disease and ulcerative colitis are the primary forms of IBD. IBD was virtually unknown until the beginning of the nineteenth century. Since then, the number of cases of this disease (as well as a number of other inflammatory diseases, including asthma) has increased dramatically in industrially developed societies. Today, at least one out of every 500 people suffers from IBD at some point in their life. This clearly indicates the key role of environmental and / or behavioral risk factors. However, people are not equally sensitive to these risk factors, predisposition to IBD has a large genetic component. Thus, it is possible to use modern genetic approaches that have recently been effective deciphering the molecular basis for the appearance of diseases and identifying new drug targets.
A genome-wide association study (GWAS) revealed more than 200 regions of the genome related to differences in sensitivity to IBD1. Before it is possible to use genetic data to better understand the disease and find new biomarkers, it is necessary to find functional genes and to hypothesize their mechanisms for influencing this disease. Unfortunately, only a small number of loci for functional variants and genes can be identified with confidence. This is typical for almost all complex diseases. The Theoretical and Applied Functional Genomics Laboratory at the Novosibirsk State University Natural Sciences Department, focused on "post-GWAS" research that connects an identified region with a biological function. The prestigious scientific journal Nature Communications published the results of this work in June 2018.
During the research that was headed by Professor Michel Georges, NSU scientists collaborated with researchers from the GIGA Institute at the University of Liège (Belgium) and the PolyOmica company to identify functional genes associated with the risk of developing IBD. Using cis-eQTL analysis, they searched for genes whose expression level was violated in people at high risk for IBD. A unique set of CEDAR data was created that includes more than 300 people with information on the expression of genes located in the region of 200 known IBD loci in nine different cell types. Using the newest methods, 99 genes were identified in 63 out of 200 IBD risk loci that are most likely directly related to IBD. This list represents a very rich source of potential new targets for drug development. To share the results with the scientific community, a CEDAR website was developed to present visual images of the results.
The screenshots of the CEDAR website are shown on the picture, which show: (a) Known risk loci for Crohn's disease. (b) HD35 risk locus with closely spaced genes and their expression. (с) Specific locus with the association pattern with IBD (black) and IL18R1 gene ex * pression (red), as well as the correlation between these patterns of associations.