After analysis of the entire human genome, more than two hundred gene locations have now been identified for the chronic bowel condition Crohn''s Disease (CD).
The identification of additional CD susceptibility genes was enabled using a mapping approach that localizes causal variants based on genetic maps in linkage disequilibrium units (LDU) maps.
Scientists at University College London (UK) have been able to identify a large number of additional genes for Crohn''s Disease, making a total of more than 200, which is more than have been found for any other disease. For example, there are just 66 known gene-regions for type 2 diabetes. The team used UK data provided by the Wellcome Trust (London, UK) which includes genetic information of 1,698 CD patients. The team''s results were also replicated using independent US data provided by the American National Institute of Diabetes and Digestive and Kidney Diseases (Bethesda, MD, USA), which contains genetic information of 813 patients with CD.
The team has provided the first clear evidence that some clinical sub-groups of patients are likely to carry different risk genes and their study shows how with a sufficiently powerful method more genes can be found in small groups of patients. This study shows how studying smaller but better-defined groups can lead to a better understanding of how complex diseases are inherited, and paving the way for personalized treatment.
The investigators confirmed 66 of the 71 previously reported loci and gave more precise location estimates for these intervals. They identified 78 additional gene regions that pass genome-wide significance, providing strong evidence for 144 genes. Additionally, 56 nominally significant signals, but with more stringent and precise co-localization, were identified. Many identified genes have functions that are compatible with involvement in immune/inflammatory processes and seem to have a large effect in individuals with extra ileal as well as ileal inflammation.
Nikolas Maniatis, PhD, the senior author of the article, said, “The discovery of so many gene locations for Crohn''s Disease is an important step forward in understanding the disease, which has a very complicated genetic basis. We hope that the method we have used here can be used to identify the genes involved in other diseases which are similarly complex, for example different cancers and diabetes." The study was published on December 13, 2012, in theAmerican Journal of Human Genetics.