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Over the last decade, the inflammatory bowel diseases (IBDs) - Crohn's disease and ulcerative colitis (UC) have been key areas of research into complex disease genetics.
More than 100 genes have been identified that increase the risk of these conditions developing, confirming that a strong genetic element is involved. Although scientists still do not understand exactly what causes Crohn’s and UC to develop, it is known that the bowel inflammation tends to arise in response to bacteria in the gut among people who are genetically pre-disposed to the conditions.
In 2006, all 22,000 genes of the human genome across 6,000 individuals were scanned by researchers. As reported in Nature Genetics, the scientists said that around 50% of the people had Crohn’s disease and the remainder did not, showing that genetics is a key element in the development of these diseases. They also said that identifying the predisposing genes could lead to the development of new treatment approaches. Several initiatives are now in place to use today’s scientific technologies and knowledge to help achieve this goal and two of these are described in more detail below.
The Crohn’s & Colitis Foundation (CCFA) has launched a project called the IBD Genetics Initiative, which involves leading scientists in the field who hope to use science and technology to discover new ways of curing or preventing the development of Crohn's disease.
To date, 165 IBD-associated genes have been identified, but their functions are not yet understood. The goals of the IBD Genetics Initiative are to:
So far, the initiative has led to the discovery of at least two gene pathways that can already be targeted using existing drugs, with one already having been confirmed as safe for use in humans.
In a world-wide collaboration over recent years, the IIBDGC has been gathering large datasets from a wide variety of countries in order to discover IBD-associated genes and also explore what the associations mean. The consortium’s latest article involved twelve groups of research analysts who used advanced statistical methods to identify patterns across the genes.
This provided new understanding about IBD risk that could not be provided by single locus analysis. Specifically, the research led to the finding that, as well as IBD genetically resembling other immune conditions, it is especially closely associated with particular inflammatory disorders such as psoriasis. The risk of IBD is not just associated with immune system changes, but with a certain subset of immune cells and signals. The risk is not only associated with susceptibility to bacterial infection, but in particular, with susceptibility to bacteria from the family that includes tuberculosis and leprosy.
The IIBDGC says that times have changed compared to five years ago, with disease gene discovery no longer being the challenging aspect; the focus of future studies should be to examine the new associations found and transform any findings into a deeper understanding of biology.