How to check your genetic data for celiac genes

Celiac disease is an autoimmune disorder in which gluten causes damage to the villi in the small intestines. Gluten is a protein found in wheat, barley, rye, and spelt. When people with celiac consume even very small amounts of gluten their body mounts a response that causes damage in the intestines.

Celiac disease is caused by a combination of environmental factors (eating gluten, other factors) and having the genetic variants that cause susceptibility to the disease. Without the genetic susceptibility, you won’t have celiac.

What is celiac disease?

Celiac disease (spelled coeliac in Britain) is an autoimmune disorder in which gluten 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:

There are a variety of symptoms associated with celiac – and not everyone with celiac will have all of the symptoms. Symptoms include:[ref]

  • gastrointestinal upset
  • tiredness/ fatigue
  • nutrient deficiencies even when eating a good diet
  • anemia or iron deficiency
  • reduced bone density, early osteoporosis
  • oral ulcers (canker sores)
  • a skin rash – dermatitis herpetiformis
  • in children, poor growth and short stature

Is celiac disease hereditary?

There isn’t one specific genetic variant that causes everyone who carries it to get celiac disease.  Instead, there are genetic variants that must be present in order for a person to be susceptible to celiac disease.  So if the variant isn’t present, you can nearly always rule out the disease.

Virtually everyone with Celiac disease has either the HLA-DQ2 or HLA-DQ8 alleles. Specifically,  90-95% of people with celiac disease have HLA-DQ2.5, and 5 – 10% of people have HLA DQ8. (Some studies also list HLA 2.2 as a possibility for Celiac as well.)

Almost 25% of the population has HLA-DQ2.5, and that percentage grows to about 30% when adding in HLA DQ8.[ref]

With only about 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 could help you rule out celiac disease, but not tell you if you have it.

***This information all comes with the disclaimer that you should always talk with your doctor for a diagnosis.  Seriously!  Your doctor can order tests such as 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; the HLA serotype is sometimes 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 through stimulating T-cells, which then signal B-cells to produce antibodies.  The 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 (blood test shows that you don’t have celiac when you actually do). 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.


What genes are associated with celiac disease?

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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 found in about 25% of European Caucasians.  So, again, 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 alone is found in about 5-10% percentage 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 .

The SNPs above cover most people with Celiac, but not quite all. The HLA-DQ2.2 variant, found by itself in a very small percentage of celiac cases, can not be completely determined with the current version of 23andMe data.


Other genes involved in celiac risk — for those who carry either HLA type from above…


Since about 1% of those with European ancestry receive a diagnosis of celiac while 30% have the HLA types for it, something else must also be involved in a person’s risk for celiac.  Recent studies have looked into other genetic traits, 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.

Below are a few of the current studies on genetic variants that add to the risk of celiac disease.

A study looked at genetic differences between over 12,000 individuals with celiac compared to approximately the same number without celiac disease. This study identified quite a few polymorphisms that influence the risk of celiac disease.[ref]

A sibling study from 2011 found three SNPs to be significant in increasing the risk of celiac disease among siblings where one sibling had been diagnosed with celiac.  The A-alleles of rs1464510, rs842647, and rs2816316 increased the risk of celiac disease in siblings — in conjunction with the HLA type.[ref]

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

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

Members: Your genotype for rs1464510 is .

 

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

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

Members: Your genotype for rs2816316 is .

A meta-analysis showed a T-allele (23andMe orientation) on rs917997  increased the 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: increased risk of celiac (with HLA type above)[ref]
  • C/T: increased 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: increased risk of celiac (with HLA type above)[ref]
  • C/T: 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:

Testing:

After learning about carrying the genetic variants linked with celiac disease, a lot of people immediately decide to try out a gluten-free diet. This can be a mistake though… For example, say that you go on a gluten-free diet and feel great. You still don’t know if you have celiac disease or if you are just gluten intolerant. It is important to know if you need to go to the extreme avoidance of gluten and watch out for cross-contamination of minute amounts of gluten or not. Most people who are gluten intolerant won’t have a terrible reaction to trace amounts of gluten. But for someone with celiac, even small amounts can still cause a problem with an autoimmune response.

Instead of jumping into a gluten-free diet, I highly suggest that you get tested first for celiac disease.  Your doctor is the place to start, and he/she can order testing for you.  If your doctor won’t order the test – or you don’t have a doctor – you can order the blood tests yourself online (UltaLab Tests – Celiac).

Increased risk of other autoimmune diseases:

People who have celiac disease are also more likely than normal to also have other autoimmune conditions such as Hashimoto’s thyroiditis and type 1 diabetes.[ref]

Learn more:

There are many resources on the internet with great information about celiac disease and the symptoms involved.  Celiac.org is a good starting point for anyone wanting to learn more.


Related Genes and Topics:

Diabetes: Genetic Risk Report
We often talk about diabetes as though it is one disease, but diabetes can have several different causes or pathways that are impacting glucose regulation. Tailoring your diabetes prevention (or reversal) efforts to fit your genetic susceptibility may be more effective.

Mast cells: MCAS, genetics, and solutions
Mast Cell Activation Syndrome, or MCAS, is a recently recognized disease involving mast cells that are misbehaving in various ways.  Symptoms of MCAS can include abdominal pain, nausea, itching, flushing, hives, headaches, heart palpitations, anxiety, brain fog, and anaphylaxis.



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.