Among the recent swath of studies associating common genetic variants with common diseases, Crohn’s disease has fared especially well. A team of international researchers has discovered 21 additional variants that not only increase Crohn’s risk, but expand understanding of how the disease works.
That amount of additional knowledge would be great news for any health condition, but it is especially welcome in Crohn’s disease. Scientists still have a lot to learn about how this inflammatory gastrointestinal disorder does its damage, and the condition is difficult to diagnose and treat.
Knowing your risk ahead of time can help speed a correct diagnosis if you develop Crohn’s symptoms. And better insights may lead to better treatments.
Understanding the importance of these new genetic findings starts with a quick look at the research to date.
It’s been known for some time that two different variants of a gene called NOD2 gene raise the risk of Crohn’s disease. In fact, these variants are double trouble for Crohn’s, because that gene affects immune cells – involved in inflammation – and cells found in the intestinal lining. In 2007, nine more susceptibility genes were discovered through the efforts of the Wellcome Trust Case Control Consortium.
The 21 new genes, recently reported online in the journal Nature Genetics take our understanding several steps further. Some of the 21 new gene variants, such as CCR6 (chemokine receptor 6) and IL12B (interleukin 12B), have known roles in autoimmunity. The functional significance of other variants isn’t yet known, but their linkage to Crohn’s disease helps point scientists in interesting new research directions.
How did the research team identify these new variants? They started by combining the data from three large genome-wide association studies. Each of these studies included thousands of people and did identify new risk variants. But only by combining them into one analysis did researchers obtain enough statistical power to identify the 21 new risk factors. Each of the 21 new risk variants has a relatively small effect, increasing a person’s risk by 8% to 50%. By comparison, the long-established NOD2 variant increases risk by 400%.
Added up, however, the new slate of markers appears to say a lot. The authors estimate that the 32 markers established to date, taken together, explain about 10% of total Crohn’s disease risk. That may be as much as one-fifth of the genetic risk.
At Navigenics, we’ll be taking a close look at this research to decide whether to include these new gene variants in our genetic health service.