A 2007 study published in the journal, Nature Genetics, identifies several different genetic regions linked to Crohn’s disease. All seem related to the body’s immune response function.

Long known to run in families, and to be more common in certain ethnic groups, Crohn’s disease has a genetic component. While researchers recognize that genetic markers are helpful in identifying who might be susceptible to Crohn’s disease, the view remains that there are also environmental triggers, or some other kind of agent, in play that activate the genes before the disease develops.

Crohn’s disease, most commonly diagnosed in people between the ages of 20 and 30, causes symptoms including abdominal pain, diarrhea, rectal bleeding, and extra-intestinal side effects such as weight loss and arthritis resulting from inflammation.

Building on the known Crohn’s-associated genetic associations of NOD2(CARD15) and IL23R, researchers from Canada and the US teamed up to delve into the human genome, searching 20,000-25,000 genes for links to this inflammatory bowel disease. Altogether, they looked at close to 2,000 individual genetic profiles where about half had Crohn’s disease. The criterion for inclusion of Crohn’s patients was that they had disease present in the ileal portion of the intestine, whether or not disease was present in other areas.

The newly identified genetic regions are:

  • strong and significantly replicated associations with an intergenic region on 10q21.1,
  • a coding variant in ATG16L1 (also confirmed by other research),
  • strong associations with independent replication to variation in the genomic regions encoding PHOX2B and NCF4, and
  • predicated gene on 16q24.1 (FAM92B).

In examining these associated genetic markers, the researchers suggest that intestinal microflora have a central role in the initiation and maintenance of Crohn’s disease. By identifying the associated genetic regions, doctors can better understand the processes behind the development of Crohn’s disease, which they hope will lead to better treatments, a cure, or even prevention.

This study relied on the Human Genome Project (HGP), an international effort from 1990-2003, to discover all the human genes and make this information accessible for further biological study. As part of the HGP, there were parallel studies on organisms such as the bacterium Escherichia coli and the mouse, to help develop the technology and interpret human gene function.

First published in the Inside Tract® newsletter issue 161 – May/June 2007
J D Rioux, R J Xavier, K D Taylor, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nature Genetics. 2007;39(5):596-604.