New Genes Associated With Crohn's Disease Defined

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A consortium of researchers from the United States, Canada, and Europe has identified 21 new genes for Crohn’s disease, a chronic disease of the large and small intestines. This discovery, funded in part by the National Institutes of Health (NIH), brings the total number of known genes associated with Crohn’s disease to more than 30 and advances understanding of causes and potential avenues to develop new treatments.

The results are reported in the advance online edition of Nature Genetics on June 29. Additional funding for the work was provided by British, Belgian, and French governmental agencies and private foundations.

As a result of the genome-wide scan, the 21 new genes strongly associated with Crohn’s were identified, including several functioning in biochemical pathways promoting inflammation, and others whose functions are still unknown. Although the biochemical functions of these variants and how they trigger inflammation in the intestines requires further study, they all represent potential targets for the development of new medications.

"The discovery of 21 new genes for Crohn’s disease highlights the importance of large genome-wide studies in determining genes responsible for some of the most common, intractable diseases that plague millions, world-wide,"said Stephen P. James, M.D., director of the Division of Digestive Diseases and Nutrition at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). "NIH will continue to support this and other genetic studies, and we are excited by the prospect of what the next series of studies may uncover."

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According to lead author Mark Daly, M.D., assistant professor of medicine at Harvard Medical School, performing the meta-analysis on the three datasets provided the statistical credibility to solidify the association of these genes to Crohn’s, and spotlights other genes, that until now, were not implicated with Crohn’s. "Exploring the functions of these proteins may offer new targets for treatment for Crohn’s"he added.

Crohn’s disease is a chronic form of inflammatory bowel disease (IBD) that usually affects the lower part of the small intestine or the large intestine (colon). The most common symptoms of Crohn’s are stomach pain and diarrhea. The disease tends to run in families and is more often diagnosed in people between the ages of 20 and 30. People of Jewish heritage, particularly Ashkenazi Jews, have an increased risk of developing Crohn’s disease.

To confirm the findings, the researchers repeated the study in 3,664 additional people with Crohn’s, unaffected family members and unaffected individuals from the general population. "There is no doubt that the analyses worked correctly and the new genes are truly associated with the disease,"said Daly.

The study, co-funded by NIDDK, was conducted by researchers from the NIDDK IBD Genetics Consortium, the Wellcome (UK) Trust Case Control Consortium and the Belgian-French IBD Genetics Consortium.

Researchers suspect that the 32 gene variants constitute only a small portion of the genes that affect Crohn’s disease. To search for more genes and unravel how these genes cause Crohn’s, researchers will need larger sample sizes. "Larger samples will also allow the investigators to figure out how particular combinations of genes influence disease risk, age of onset, disease severity, and response to treatment,"noted Robert W. Karp, Ph.D., project scientist for NIDDK’s IBD Genetics Consortium in the Division of Digestive Diseases and Nutrition.

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