New Genetic Risk Factors Identified in Crohn's Disease

Massachusetts researchers have identified several novel genetic risk factors involved in Crohn's Disease (CD), a chronic inflammatory bowel disease that affects about half a million people in the U.S. alone, with another half million Americans affected by a related condition called ulcerative colitis. While no single causative factor has been identified, CD has a tendency to run in families and certain ethnic groups, arguing for a genetic component to this disease. Symptoms of CD include abdominal pain and chronic diarrhea, leading to ulceration, bleeding, and even the development of fistulas (interconnections between the intestine and other organs), leading to severe infection.

Previous studies of CD identified a possible causative genetic variant on chromosome 16. However, this mutation accounts for only a small percentage of CD cases. In 2001, researchers at the Whitehead Institute identified another gene, called IBD5, and located on chromosome 5, as another possible culprit. The region surrounding IBD5 had been found important in other inflammatory diseases, such as lupus and asthma, making IBD5 a much more significant agent in CD. While IBD5 genetic variation was found to be a causative agent in CD, the genetic variation itself was the result of single nucleotide polymorphisms (SNPs), or the single letter DNA differences found between individuals, many of which are implicated in various genetic diseases. The possibility that SNPs are culprits in many diseases provided the impetus to create a genome-wide map of such SNPs, called the HapMap.

In a report soon to be published in the journal Nature Genetics, researchers from the Massachusetts General Hospital, Broad Institute of Harvard University, and Massachusetts Institute of Technology report that, using the HapMap as their guide, SNPs in two additional genes, plus a region that is gene-free, were found strongly associated with CD. Furthermore, three additional SNPs, contained within three other genes, were also found to be risk factors for CD.