My family is like many you hear about in which celiac disease travels through the family tree. But in some other families there seems to be just one “rogue” case, and no one knows where it came from.

As I recently learned, the genetics of this autoimmune disorder can be confounding.

Celiac disease can be passed down through the generations. The University of Chicago’s Celiac Disease Center reports that if a family member is diagnosed with celiac disease there is a one in 20 chance that a first-degree relative—a parent, child or sibling—will also get celiac disease. That prevalence drops to one in 39 for second-degree relatives such as aunts, uncles and grandparents.

How does celiac disease run through families?

I have been giving that topic a lot of thought lately. My brother and my daughter have confirmed cases of celiac disease. My father carries a gene for it but started a gluten-free diet at a doctor’s request before getting the blood antibody test for celiac disease. He remains gluten free to this day. His aunt also was diagnosed with celiac disease and lived with it for 40 years before her death in the 2000s.

Because of my family history, I get my blood tested for celiac disease antibodies every few years. But I started wondering why celiac disease hasn’t reared its ugly head with me just yet.

I assumed I did not need a genetic test for the disease because, of course, I was the gene carrier. I have felt this way for more than a decade.

Then something changed. I was worried I had celiac disease but was asymptomatic. I didn’t want to find out years from now that I had the condition all along and could have prevented the negative effects of untreated celiac disease.

A few months ago, I had the blood tests for celiac disease done again. Negative. Then I had the biopsy done. Negative. All that was left was the gene test.

I thought I knew what the result would be. But I did it anyway. And what happened next shocked me to my core.

“The celiac gene test came back negative. You do not have HLA-DQ2 or DQ8,” the lab report said.

How is that possible? How can a person have such a strong family history of celiac disease and not have the related gene?

The genetics behind celiac disease

Thirty to 40 percent of people in the United States have one or both of the genes called HLA-DQ2 or DQ8, which are the ones associated with celiac disease. The National Institutes of Health says only about 3 percent of those with the genes actually get celiac disease.

The HLA (human leukocyte antigen) molecules help decide whether your body will have an immune response. HLA molecules hold onto protein, foreign or not, and show it to a deciding white blood cell, which figures out whether to attack it or let it go, says Daniel Leffler, M.D., director of research at the Celiac Center at Beth Israel Deaconess Medical Center in Boston, Massachusetts, and associate professor of medicine at Harvard University. While the human body has many HLA molecules, the only ones that can bind onto gluten tightly enough to get the immune system excited are DQ2 and DQ8, Leffler says.

Testing negative for the genes rules out celiac disease in virtually all cases, but testing positive does not mean you have celiac disease. A trigger is still needed to activate the disease in your body.

Genetic testing for celiac disease is still uncommon. Leffler says the gene test is done in only about 20 percent of the cases at the Beth Israel Deaconess Celiac Center. But he suspects the percentage of people being genetically tested at a typical gastroenterologist’s office is even lower.

The ins and outs of testing

I didn’t get my family tested for the genes because I thought I would recognize the symptoms of celiac disease if they occurred, based on my familiarity with the disease. But there are other reasons families don’t get the genetic test.

Insurance costs are a big concern. Sometimes the test is covered and sometimes it isn’t. Mine was covered because I was seeing a gastroenterologist. But my daughter who does not have celiac disease was denied coverage for testing because she wasn’t seeing a gastroenterologist.

David Flannery, M.D., medical director of the American College of Medical Genetics and Genomics in Bethesda, Maryland, says there are a few reasons insurance doesn’t cover gene testing. First an insurance plan might not include genetic testing in its coverage.

Second if there is no drug or surgical treatment for the health condition the gene might be connected with, insurance companies may not cover it. And often, Flannery says, smaller labs conducting genetic testing are out of network. “Cost is a barrier,” Flannery says. “It’s becoming a bigger and bigger issue. At some point I see patient advocacy groups getting in on this.”

But there may be an answer for patients who can’t get insurance coverage for the test. If the price of the test is a concern, Leffler says direct-to-consumer swab tests for HLA-DQ2 and DQ8 genes are readily available and reliable. “It might be worth doing yourself,” he says.

Physicians on the front line of patient care can be another barrier if they are not knowledgeable about genetic testing. “That is what I have heard is the biggest issue. You don’t even get to the insurance part. Physicians are just reluctant and don’t know what to do with [genetic testing],” Leffler notes.

Flannery agrees. “Lack of knowledge of non-genetic physicians goes two ways. Some don’t know about genetics, never heard of it, don’t know how to find out about it and are too busy to find out,” he says. “Another way is that the doctors over-test, which may not be necessary.”

Getting a referral to a celiac disease center in your area or state can be the quickest way to get genetic testing through a physician.

While some patients are frustrated that they can’t get tested, others are concerned about having a genetic result on their health record, with its implications at school or work or when getting new health insurance coverage. “Fortunately the GINA [Genetic Information Nondiscrimination Act] law protects that information,” Flannery says. The U.S. Equal Employment Opportunity Commission explains that GINA makes it “…illegal to discriminate against employees or applicants because of genetic information.”

Providing answers for your family

A genetic test does not tell you if you or someone in your family has celiac disease. But it can be an important first step that, if positive, should be followed by blood tests and a biopsy.

In my case getting the test results changed my personal outlook on celiac disease. Before I had the test, I was always looking over my shoulder, wondering if having a baby, hitting menopause or just getting a bad virus would trigger celiac disease.

My negative test result ruled out the possibility of celiac disease, and I no longer have to have periodic blood work to make sure the disease is not developing.

“It is worth knowing if a person is at risk for celiac,” Leffler says. It can be especially important for children with first-degree relatives because it gets them “off the hook” in relationship to celiac disease, he explains. In families with several children it’s likely one or more will be negative, and it can save years of worrying whether they have or will develop the disease.

Meanwhile a positive gene test result could increase awareness of symptoms, eating habits and triggers in children, which are important in catching the disease early. Recent studies show that children who have multiple copies of DQ2 are at higher risk for getting celiac disease. “As a parent, you may be more vigilant with a child who has two copies of DQ2 than a child with one copy of DQ8,” Leffler says.

Also DQ2 is the gene that is shared by those who have celiac disease and Type 1 diabetes. If you have one condition, Leffler says, you may have the other. This may also be true with autoimmune diseases such as autoimmune thyroid disease and Hashimoto’s thyroiditis.

Skipping a generation?

But how can the celiac disease genes seemingly skip me and go to my daughter? Or in another family, how can the gene be nonexistent until celiac disease suddenly pops up in a single family member?

It is not as simple as it seems. HLA-DQ2 is actually four genes, and HLA-DQ8 is two genes. The gene that is handed down to the next generation could impact the likelihood of developing celiac disease.

Both parents can have the genes for celiac disease, and their child can luckily only inherit the part of the genes that aren’t connected with the condition. “This is unlike most genetic disorders. You can have two parents who are negative and a child who is positive and it can bounce around in odd ways for sure,” Leffler says.

If you have the gene and the potential for celiac disease to develop, there isn’t much you can do to prevent it. Recent studies have debunked the theory that timing of gluten introduction and breastfeeding in infants may be ways to keep celiac disease at bay.

Flannery says some people preemptively go on a gluten-free diet. Since the gene does not automatically mean a person will develop celiac disease, this is not generally recommended. The gluten-free diet prevents a definitive diagnosis of celiac disease.    

 Genetic testing for celiac disease can be hard to initiate and costly. But the information you get could help you in the long run. “For family members at risk of celiac [disease] but [who] don’t yet have it, [the test] can be very helpful information,” Leffler says.

At-home genetic tests

You can take a test to determine whether you have the genes for celiac disease with several products designed for home use.

Typically you swab the inside of your cheek and send the swab to the test center, which will return lab results to you or your physician.

These tests will not tell you if you have celiac disease, but will alert you if you have the genes associated with development of the disease. All test companies note that a positive result should be followed up with your physician.

Also tests for the genes are still accurate if you are already on a gluten-free diet. This differs from blood antibody tests that are used to diagnose celiac disease, which may not be accurate if the diet has already been started.

• Kimball Genetics: kimballgenetics.com/submitind.html?pid=5
  Price: Detailed when you contact the company
• Glutenpro: glutenpro.com/genesure.html
  Price: $190
• Request A Test: requestatest.com/celiac-genetic-test?gclid=CJCsqP2xiMUCFcSIaQod3I0AOw
  Price: $599

Related articles

Are Bacteria to Blame?

Neurological Symptoms of Celiac

Is the Biopsy Still the Gold Standard for Diagnosing Celiac?