By Jonathan Hansen, MD, PhD
Genetic testing in laboratory. Test for Crohn's disease, ulcerative colitis, inflammatory bowel disease, IBD

Your family of origin often has a lot to do with your health, between giving you your genetic makeup and providing the environment in which you grew up, all of which can have an effect on whether you develop IBD.

We know that inflammatory bowel diseases (IBD, including Crohn’s disease and ulcerative colitis) are caused by many different things, including the genes you were born with and the environments you have lived in. Researchers have worked hard to learn how these two factors might cause IBD, and they have made a lot of progress, especially in discovering genetic mutations that are connected with IBD.

However, despite this massive amount of new information about genes and IBD, it is still unclear how to apply it to individual people with IBD.

High-Tech Tools to Test DNA

New high-tech tools have made it possible for us to learn about the genes that might cause IBD. These tools essentially take small snapshots of a person’s DNA at a lot of different spots, and then they use these snapshots to predict what the rest of the DNA looks like. In this way, scientists can get a general idea of what is in a person’s genome without having to look in detail at every part of the DNA.

Genes in IBD

When researchers applied this tool to about 60,000 people, they identified more than 240 DNA segments that were more likely to be different in people with IBD than in “healthy people.”

If the difference in each of these 240 DNA segments affects one gene, then we could predict that more than 240 genes are associated with IBD. That’s a lot of genes!

Using this technique, researchers have identified just one gene called NOD2 that has, by far, the strongest connection to IBD. It’s important to note that this gene is connected with Crohn’s disease, but not ulcerative colitis.

Can Genetic Tests Predict Whether I Will Develop IBD?

What role does genetic testing play in diagnosing or managing IBD? The short answer right now is: Very little. Here’s why.

Humans have two copies of each gene, one from Mom and the other from Dad. If, for example, a person has the particular mutation in both copies of their NOD2 gene (the one that has the strongest connection with IBD), then their risk of developing Crohn’s disease is about 20 times higher than someone who doesn’t have this mutation in both of their NOD2 genes.

Another way of looking at it is that mutations in both copies of NOD2 increase the risk of developing Crohn’s from about 3 in 1,000 (the risk of Crohn’s in the general population) to 60 in 1,000. That’s a big jump!

But note that out of that same 1,000 people, there are still 940 with mutations in both copies of their NOD2 genes who do not develop Crohn’s disease.

This same phenomenon is seen with the other 239 IBD-associated DNA segments, too.

What this means is that the vast majority of people who carry an IBD-associated piece of abnormal DNA will never develop IBD!

IBD doctor, gastroenterologist reviewing Crohns Ulcerative Colitis patient record

Should You Get Tested?

With the above information in mind, it’s easy to see that genetic tests to predict who might develop IBD are not very helpful.

Nonetheless, some companies have advertised directly to the public that they can test a person’s DNA to predict the risk of all sorts of diseases. Because the accuracy of using such tests to identify disease risk in the general population is unclear, and because a false positive test can cause unnecessary stress to a person, the FDA has instructed these companies to stop marketing their genetic tests in this manner.

This move is supported by the fact that, 3 out of 5 times, this type of genetic test incorrectly predicted whether or not a person would develop IBD.

Can Genetic Tests Predict Complications?

If genetic testing can’t be used to adequately predict who will develop IBD, can it be used to predict the severity of IBD in someone who has already been diagnosed?

Again, the short answer is: No.

A few small, preliminary studies have shown that gene tests can somewhat predict which ulcerative colitis patients will go on to develop severe, medication-resistant disease, or which Crohn’s patients will go on to require surgery. However, these studies need to be repeated with larger groups of patients to see if these genetic tests really work before they can be used in patient care.

What About Response to Treatments?

What about using genetic testing to predict who might respond to certain IBD medications? This actually is already being done, to a limited extent:

  • Testing for mutations in the thiopurine methyltransferase gene can help doctors decide how to best use a class of medications called thiopurines to treat IBD.
  • Some studies also have identified a few gene mutations that might predict which IBD patients respond better to anti-TNF therapy (including Remicade, Humira, Cimzia, Simponi), but these studies also need to be repeated with more people before the tests can be used in patient care.

Where We Stand Now

Over the past 15 years, we’ve learned a lot about the genes that are connected to IBD. This information will no doubt lead to better treatments and information for patients in the future. But, for the time being, clinical application of genetic testing in IBD patients is mostly still experimental.

Author and Oshi physician-partner Jonathan Hansen, MD, PhD, has been involved in 20-plus clinical trials of investigational compounds that target various pathways important in the development of IBD. He has co-authored book chapters on IBD and been published in a variety of peer-reviewed journals, and his interests include the role of environmental bacteria in the development of chronic intestinal inflammation. Dr. Hansen serves as an Associate Professor of Medicine in the Division of Gastroenterology & Hepatology at the University of North Carolina at Chapel Hill. He received his BS in Biochemistry from Brigham Young University, and his MD and PhD in Microbiology and Immunology from Indiana University School of Medicine.

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