The Genetics of Celiac Disease

Celiac disease is genetic, but the genetics are complicated. Having the genes doesn’t mean you’ll develop celiac. Not having them essentially guarantees you won’t.

Here’s what the genetics actually mean.

The Required Genes: HLA-DQ2 and HLA-DQ8

Celiac disease requires specific genes called HLA-DQ2 or HLA-DQ8. These are part of the human leukocyte antigen (HLA) system, which helps your immune system distinguish self from non-self.

HLA-DQ2: Present in about 95% of people with celiac disease. The main genetic risk factor.

HLA-DQ8: Present in most of the remaining 5% of celiacs (and some have both).

Without one of these genes, celiac disease is essentially impossible.

The Paradox: Common Genes, Uncommon Disease

Here’s what’s confusing:

• About 30-40% of the general population carries HLA-DQ2 or DQ8
• Only about 3% of people with these genes develop celiac disease
• Overall celiac prevalence is about 1% of the population

The genes are necessary but not sufficient. Most people with the genes never develop celiac.

What Else Matters?

If genes aren’t everything, what determines who develops celiac?

Environmental triggers: Something has to “turn on” the disease in genetically susceptible people. Possibilities include:

• Infections (particularly gut infections)
• Gut microbiome composition
• Age at gluten introduction
• Amount of gluten consumed
• Stress or other triggers

Other genetic factors: There are likely additional genes beyond HLA that influence risk. Research is ongoing.

Unknown factors: We don’t fully understand why one person with HLA-DQ2 develops celiac and another doesn’t.

Family Risk

If you have celiac disease, your family members are at increased risk.

First-Degree Relatives (Parents, Siblings, Children)

• About 10% will have or develop celiac disease
• Compared to 1% in the general population
• Should be screened even without symptoms

Second-Degree Relatives (Grandparents, Aunts, Uncles, Nieces, Nephews)

• Elevated risk but less than first-degree relatives
• Screening recommended if symptomatic

Identical Twins

• If one twin has celiac, about 75% chance the other will too
• Not 100%, which shows environment matters too

Will My Kids Have Celiac?

If you have celiac disease:

Your child definitely inherited at least one of your HLA genes. They have at least the possibility.

The actual risk is about 10%. Most children of celiacs don’t develop it.

Early symptoms may be subtle. Growth issues, irritability, GI problems.

Screening is recommended. Typically starting around age 3 if eating gluten, and periodically if negative.

Testing Your Family

Genetic Testing

• Tests for HLA-DQ2 and DQ8
• If negative, celiac is essentially ruled out
• If positive, doesn’t mean they have or will get celiac, just that they could

When genetic testing helps:

• Ruling out celiac definitively (if negative)
• Deciding whether to pursue further screening
• When someone is already gluten-free (antibody tests require eating gluten)

Antibody Testing

• tTG-IgA and other blood tests
• Must be eating gluten for accurate results
• If positive, suggests active celiac
• Should be repeated periodically even if initially negative (can develop later)

Recommended Screening Protocol

For first-degree relatives:

1. Antibody testing (while eating gluten) starting around age 3
2. Repeat every 2-3 years even if negative, especially if symptoms develop
3. Genetic testing to determine if continued monitoring is needed

If HLA-DQ2/DQ8 negative: essentially no risk, no further screening needed If HLA-DQ2/DQ8 positive: continue periodic antibody screening

If a Family Member Tests Positive

If a relative’s screening shows elevated antibodies:

• Referral to gastroenterologist
• Biopsy to confirm diagnosis
• Begin gluten-free diet if confirmed

Catching celiac early, before significant damage, leads to better outcomes.

Communicating with Family

Having celiac means having potentially important information for your family. Consider:

Telling relatives about their risk:

“Celiac disease is genetic and runs in families. First-degree relatives have about a 10% chance. You might want to talk to your doctor about screening.”

Providing resources:

• Information about celiac screening
• What symptoms to watch for
• How to request testing

Respecting their choice: Some relatives won’t want to be tested or won’t take it seriously. You can inform; you can’t force.

The Bigger Genetic Picture

Celiac disease is one of the most heritable autoimmune conditions. If you have it:

• It’s not random chance, it’s in your genes
• It’s not your fault, you inherited these genes
• It informs family planning (your kids will need monitoring)

For People Considering Genetic Testing

Reasons to test yourself (if already GF):

• Confirm whether you carry HLA genes (helps confirm diagnosis)
• If negative, celiac is unlikely (though not impossible if you have other risk genes)

Reasons to test children or siblings:

• Rule out celiac if negative (no further screening needed)
• Identify who needs ongoing monitoring if positive

Insurance considerations:

• Genetic testing results could theoretically affect insurance
• In practice, HLA-DQ2/8 testing for celiac is usually not a major concern
• Consult with a genetic counselor if worried

The Future

Research continues on:

• Other genetic risk factors beyond HLA
• Why some people with genes develop celiac and others don’t
• Potential genetic therapies (far-future)

Understanding genetics helps us understand the disease. Eventually, it may help prevent or treat it.

For now, knowing your genetic status helps with screening decisions and family planning.

The Bottom Line

Celiac disease is genetic:

• Requires HLA-DQ2 or DQ8 genes
• But most people with these genes don’t develop celiac
• First-degree relatives have ~10% risk
• Genetic testing can rule out celiac if negative
• Antibody screening should be periodic for at-risk relatives

Your genes determined your risk. They also give you information to share with your family.