Celiac Disease Genes: How to Check Checking

Key takeaways:
~ Celiac disease is an autoimmune disorder in which gluten causes damage to the small intestines.
~ Celiac is only possible in people with specific HLA genotypes.
~ You can use your genetic raw data (23andMe, AncestryDNA, etc) to find out if you have the HLA type that makes you susceptible to celiac.

Members will see their genotype report below, plus additional solutions in the Lifehacks section. Consider joining today.

Table of Contents

What is celiac disease?

Celiac disease (spelled coeliac in Britain) is an autoimmune disorder in which gluten, a protein found in wheat and other grains, leads to your body attacking its own cells.

Inside the small intestines, there are little projections called villi. In celiac disease, the body attacks those cells, causing the villi to shorten and not absorb nutrients very well.

Symptoms of celiac disease:

Symptoms of celiac disease can vary from person to person, but some common ones include: [ref]

Gastrointestinal issues
Tiredness or fatigue
Nutrient deficiencies even when eating a good diet
Anemia or iron deficiency
Reduced bone density and early osteoporosis
Canker sores
Dermatitis herpetiformis (itchy skin rash)
In children, poor growth and short stature

It’s also worth noting that not everyone with celiac disease will have all of these symptoms.

Is celiac disease hereditary?

Genetic diseases that are hereditary are caused by inheriting a genetic variant or mutation from your parents.

While there isn’t just one specific genetic variant that causes everyone who carries it to get celiac disease, it is hereditary and based on genetic variants.

In order for a person to be susceptible to celiac disease, certain genetic variants must be present. If these specific variants, called HLA alleles, are not present, it is highly unlikely that a person has celiac disease.

Almost everyone with Celiac disease has either the HLA-DQ2 or HLA-DQ8 alleles.

90-95% of people with celiac disease have HLA-DQ2.5
About 5 – 10% of people have HLA-DQ8.
Some studies also list HLA-DQ2.2 as a possibility for celiac, with about 1% of celiac patients carrying HLA-DQ2.2.

It’s important to understand that not everyone who has these HLA types will develop celiac disease. In fact, almost 25% of the population has HLA-DQ2.5, and that percentage grows to ~30% when adding in HLA-DQ8 alleles.[ref]

With only ~1% of the population having celiac disease, you can see that just having the HLA type doesn’t mean that you will get celiac disease.

Thus, looking at your genetic variants can help you rule out celiac disease, but it cannot tell you if you have it.

With genetics as only part of the picture, other testing is needed. Talk with your doctor for a diagnosis. Your doctor can order tests such as a blood test or a small intestine biopsy to accurately diagnose or rule out celiac disease.

What is an HLA serotype?

Serotypes, discovered in 1933 by Rebecca Lancefield, are variations within species (bacteria and viruses) or variations among immune cells in people. The typing is based on their cell surface antigens. In humans, the human leukocyte antigen (HLA) determines the serotype. HLA serotypes can be used in determining transplant matches.

One HLA type is HLA-DQ, which is a protein found on antigen-presenting cells. DQ is involved in the immune system by stimulating T-cells, which then signal B-cells to produce antibodies.

HLA-DQ recognizes foreign antigens from pathogens, but it also recognizes common self-antigens. This is where the problem begins when the HLA-DQ loses its tolerance to self-proteins, triggering autoimmune diseases such as celiac, lupus, and type 1 diabetes.

Diagnosing Celiac Disease:

There are blood tests that can show whether you carry antibodies against gluten. The test is not 100% accurate, and some people may have false-negative results (e.g., a blood test shows that you don’t have celiac when you do).

Genetics can help you rule out celiac disease. If you don’t carry the HLA type (below) and also have a negative antibody test, then celiac is highly unlikely.

The ‘gold standard’ is an intestinal biopsy, where a gastroenterologist takes a small snip out of your intestines to see if there is damage to the villi.

Celiac Genotype Report

Members: Log in to see your data below.
Not a member? Join here. Membership lets you see your data right in each article and also gives you access to the member’s only information in the Lifehacks sections.

New! Printable Overview Report (Members)

HLA-DQ2.5:

Approximately 90-95% of celiac patients have HLA-DQ2.5, which can be determined by looking at rs2187668 (T).[ref] This genetic variant is fairly common and is found in about 25% of European Caucasians. Thus, having the genetic variant does not mean that you have celiac, only that it is possible for you to have it or develop it at some point.

Check your genetic data for rs2187668 (23andMe v4, v5; AncestryDNA):

C/C: typical (no risk for celiac unless HLA-DQ8)
C/T: one allele for HLA-DQ2.5 (Celiac disease is possible)
T/T: two alleles for HLA-DQ2.5 (Celiac disease is possible)

Members: Your genotype for rs2187668 is —.

HLA-DQ8:

HLA-DQ8 alone is found in about 5-10% of Celiac patients.

Check your genetic data for rs7454108 (23andMe v4, v5; AncestryDNA):

C/C: two alleles for HLA-DQ8 (Celiac disease is possible)
C/T: one allele for HLA-DQ8 (Celiac disease is possible)
T/T: typical (no risk for celiac unless HLA-DQ2)

Members: Your genotype for rs7454108 is —.

HLA-DQ2.2:

The SNPs above cover most people (~98%) with Celiac, but not quite all. The HLA-DQ2.2 variant is found in 1-2% of people with celiac disease.[ref][ref]

To determine your HLA-DQ2.2 status, you must have all three of the following risk alleles listed as “HLA-DQ2.2 possible”.

Check your genetic data for rs4713586 (23andMe v5, AncestryDNA):

A/A: HLA-DQ2.2 possible if you also have rs2395182 T, and rs7775228 C
A/G: not HLA-DQ2.2
G/G: not HLA-DQ2.2

Members: Your genotype for rs4713586 is —.

Check your genetic data for rs2395182 (23andMe v4, v5, AncestryDNA):

T/T: HLA-DQ2.2 possible if you also have rs4713586 A/A, and rs7775228 C
G/T: HLA-DQ2.2 possible if you also have rs4713586 A/A, and rs7775228 C
G/G: not HLA-DQ2.2

Members: Your genotype for rs2395182 is —.

Check your genetic data for rs7775228 (23andMe 4, v5; AncestryDNA):

C/C: HLA-DQ2.2 possible if you also have rs4713586 A/A, and rs2395182 T
C/T: HLA-DQ2.2 possible if you also have rs4713586 A/A, and rs2395182 T
T/T: not HLA-DQ2.2

Members: Your genotype for rs7775228 is —.

Other genes involved in celiac risk (only for people who carry the HLA type from above):

The HLA genotypes (above) are necessary for celiac disease, but they aren’t the only factors involved. Recent studies have looked into other genetic variants, as well as environmental aspects such as duration of breastfeeding, the timing of the introduction of wheat to an infant’s diet, and types of bacteria in the gut.[ref][ref]

SH2B3 gene: encodes a lymphocyte adapter protein that regulates signaling pathways related to inflammation.

Check your genetic data for rs3184504 (23andMe v4, v5; AncestryDNA):

C/C: typical
C/T: increased relative risk of celiac (with HLA type above)
T/T: increased relative risk of celiac (with HLA type above)[ref][ref]

Members: Your genotype for rs3184504 is —.

LPP gene:

Check your genetic data for rs1464510 (23andMe v4 only):

A/A: increased relative risk of celiac (with HLA type above)[ref]
A/C: increased relative risk of celiac (with HLA type above)
C/C: no increased risk

Members: Your genotype for rs1464510 is —.

TAGAP gene:

Check your genetic data for rs1738074 (23andMe v4; AncestryDNA):

T/T: increased relative risk of celiac (with HLA type above)[ref]
C/T: increased relative risk of celiac (with HLA type above)
C/C: no increased risk

Members: Your genotype for rs1738074 is —.

REL gene:

Check your genetic data for rs842647 (23andMe v4; AncestryDNA):

A/A: increased relative risk of celiac (with HLA type above)[ref]
A/G: increased relative risk of celiac (with HLA type above)
G/G: no increased risk

Members: Your genotype for rs842647 is —.

Check your genetic data for rs2816316 (23andMe v4, v5):

A/A: increased relative risk of celiac (with HLA type above)[ref]
A/C: increased relative risk of celiac (with HLA type above)
C/C: no increased risk

Members: Your genotype for rs2816316 is —.

IL-18 receptor: A meta-analysis showed a T-allele (23andMe orientation) on rs917997 increased the relative risk of celiac disease by 5%, The same study showed a T-allele on rs6441961 increased the risk of celiac by 6%.[ref]

Check your genetic data for rs917997 (23andMe v4, v5; AncestryDNA):

T/T: slightly increased relative risk of celiac (with HLA type above)[ref]
C/T: slightly increased relative risk of celiac (with HLA type above)
C/C: no increased risk

Members: Your genotype for rs917997 is —.

Check your genetic data for rs6441961 (23andMe v4, v5; AncestryDNA):

T/T: slightly increased risk of celiac (with HLA type above)[ref]
C/T: slightly increased risk of celiac (with HLA type above)
C/C: no increased risk

Members: Your genotype for rs6441961 is —.

A Finish study from 2012 found that FUT2 non-secretors are at an increased risk of celiac disease. The A/A genotype for rs601338 determines a non-secretor. The odds ratio for non-secretors for celiac is 1.28. (Non-secretors are also resistant to the Norovirus.)

Check your genetic data for rs601338 (23andMe v4, v5):

A/A: increased risk of celiac
A/G: no increased risk
G/G: no increased risk

Members: Your genotype for rs601338 is —.

Lifehacks:

The rest of this article is for Genetic Lifehacks members only. Consider joining today to see the rest of this article.

Member Content:

An active subscription is required to access this content.

Join Here for full access to this article, genotype reports, and much more!

Already a member? Log in below.

Celiac Genes: How to Check Your Raw Data