How to Read Celiac Genetic Report

How to Read Celiac Genetic Report

Anil Kumar, PhD
Jun 15 2020 19:55

Before we start

Ordering a celiac genetic test is a big step towards learning about your genetic risk. If you have already taken this step, congratulations! If not, the information below should help you make a decision.

An example of celiac genetic test report


First, a certain amount of technical jargon should be expected. For example, results might be described as ‘probability’, ‘risk of 1 in 100’, 'percentage' or as ratios such as '1:100'. At first, this is understandably frustrating. But, in reality, what this really means is your risk relative to the general population. For example, the risk of celiac disease in US and Western Europe is about 1% or 1 in 100 people. If your results show 0.5% (or 5 in 1,000--which is effectively 1 in about 200 people), you are at lower risk than an average person.

Research in understanding the role of genes is growing rapidly. That's why it is such an exciting time to learn about genes and how they impact our health.

How much genes impact our health?

Genes are not the only factors determining our health. For celiac, at least 4 out of 5 conditions need to be satisfied for a confirmed diagnosis of celiac disease. The presence of genes is a must, but there is no guarantee that you will have celiac if the genes are found. In fact, most people live a normal healthy life despite testing positive for certain celiac genes.

A recent Harvard study looked at data of 40 million Americans and concluded that, at most, genes could only explain about one-third of their health conditions. Often, more than one gene might be responsible. What if that secondary gene is not even discovered yet?

Our knowledge of genes is growing rapidly. Today, the presence of a gene can be determined with very good accuracy. And the technology is becoming powerful and less expensive over time.

Confirmation of a particular gene might help us make better decisions about health. For example, when sensitivity to a particular food is observed–gluten in the case of celiac–finding out what the responsible genes do to trigger this reaction allows us to appreciate the importance of health recommendations, such as gluten-free diet.

In the example below we will walk you through to show how genes trigger such an adverse response. And how inheriting few genes might result in getting sick from something as common as wheat, which billions of people eat everyday.

What is a simple way to explain genes and our genome?

If human genetics were compared to a book, it will have two volumes and each parent will provide one of them. There will be 23 chapters (same as 23 chromosome pairs) and half of each chapter will be written by their mother and another half by their father. A page in this ‘book of life’ will be analogous to a gene.

Here is an easy, simple way to look at our genes:


What are chromosomes?

In the ‘book of life’, the 23 chapters are the chromosomes. They always occur in pairs as shown in the image below, each parent contributing one arm of this pair. The celiac genes (or pages containing information about celiac sensitivity) are on chromosome six (or chapter 6 of the ‘book of life’).

Here is an image showing the 23 chromosomes. Celiac genes are on chromosome # 6:


What are celiac genes?

Genes are equivalent to pages in the ‘book of life’. Inside chapter 6, two pages carry the information necessary to make proteins that bind to gluten to cause gluten sensitivity. The sub-chapter or section (or ‘HLA region’ in genetic terminology) that carries the code for gluten reaction is on the short arm of this chromosome. The DQ HLA regions are the ‘pages’ specific to celiac. Your celiac genetic test report tells whether you have these pages or not.

Celiac genes on chromosome # 6, marked as DQ on HLA region:


How celiac genes cause gluten intolerance?

The DQ ‘pages’ in the ‘book of life’ make the protein that binds with gluten. This binding is necessary for immune cells to respond and cause gluten allergy. It’s important to note: if you don’t have appropriate pages in the ‘book of life’, you can’t make the protein that eventually results causing the allergy.

The protein, that binds to gluten, is a dimer (meaning it has two arms). Both arms can be made in several different ways:

1. One arm (α chain) is made by the DQ ‘pages’ of dad’s chapter and another arm is made by mom’s chapter (β chain); or

2. Both arms are made by mom’s pages; or

3. Both arms are made by dad’s pages

When the same gene appears on both chromosomes (or both ‘chapters’ of the ‘book of life’, it’s called homozygosity. This might have additional impact, e.g., in celiac it further increases the risk.

Here is an example when both parents have the genes to form the gluten binding DQ2 dimer molecule:

An example where one parent (e.g., mom) has both genes to form the gluten binding dimer molecule:


Same example as above where dad has both genes to form the gluten binding dimer molecule:


In 5-10% cases, a different ‘page’, the DQ8 gene (instead of DQ2) might form the dimer (more specifically, as DQA1*03 and DQB1*03):


What happens if you don’t have the celiac genes?

You may have the celiac genes but no gluten allergy. The reasons for this are not yet completely understood.

However, it is extremely rare (0.04%) to have celiac disease without the relevant genes. That's why, a negative result for celiac genes is extremely valuable.

Without the celiac genes, no dimer is formed to bind with gluten and show sensitivity to gluten:


Frequently asked questions on celiac:

Q: Do I need to be on a gluten-free diet to test?

A: No. The genes do not change whether you are currently eating gluten or not. The test can be done any time.

Q: Can I test my children? Is there an age limit to test?

A: As long as a parent or guardian is ordering the test, we can test all ages.

Q: What is the sensitivity and specificity of the test?

A: The sensitivity (truly identifying those who are positive) and specificity (truly identifying those who are negative) are more than 99%.

Q: If my results are positive, does that mean I have celiac disease?

A: Presence of the DQ2 and DQ8 celiac genes does not mean you will have the celiac disease. The reasons are not yet understood. However, if you do NOT have the genes, it’s almost certain you will NOT have celiac disease (life-time risk of celiac without the genes is 0.04%).

Q: My family has a history of celiac disease but not everyone is gluten intolerant. Should I still take the test?

A: About 1 in 100 people in US and Europe have celiac disease. But it clusters around families as almost 50% of first-relatives have the genes that may cause gluten intolerance. Also, not everyone is diagnosed (that’s why the silent/invisible cases result in so called ‘celiac iceberg’).

Q: How does homozygosity affects my results?

A: When both parents have the celiac genes, they are homozygous (otherwise heterozygous). This tends to increase the risk.

Q: What if I have more questions?

A: We have reviewed the current research on celiac and summarized the findings in FAQs, historical evidence, and reviewed the research on genetic risk. If you have more questions about your celiac genetic report, you can always contact us.