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Genetic and Rare Diseases Information Center (GARD)

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Celiac disease

*

* Not a rare disease

Other Names for this Disease

  • Celiac sprue
  • Coeliac disease
  • Gluten intolerance
  • Gluten-induced enteropathy
  • Gluten-sensitive enteropathy
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

I'm trying to make sense of my genetic test results for celiac disease. I carry both the HLA-DQ2 and HLA-DQ8 genes. I understand what Punnett squares are and all that, but I'm trying to figure out the probability of my daughter inheriting one of these genes. It would be 100% for one of them, correct? Her father hasn't been tested but he displays some celiac-like symptoms so he may carry one or two genes for celiac. I understand that 40% of the population carries celiac genes and that 1 in 100 develop celiac. I'd really like to see this explained by use of a Punnett square.

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

Is celiac disease inherited?

Susceptibility to developing celiac disease (CD) can be inherited, but the disease itself is not inherited. Celiac disease is a multifactorial disorder, which means that multiple genes interact with environmental factors to cause CD. The condition is due to the interaction of the genes HLA-DQA1 and HLA-DQB1 (known to be associated with CD susceptibility); non-HLA genes that are less well-understood; gliadin (a component of gluten); and other environmental factors.[1] While multifactorial disorders can run in families, they generally do not follow a specific inheritance pattern.

The risk for a relative of an affected person to develop CD is mostly based on empiric risk data. This means that the risk is assumed based on what has been reported, and the experiences of many families with affected people. However, genetic testing of the genes that cause susceptibility to CD can help people get a more personal risk assessment. For example, when the genetic status of an affected person's child is unknown, the child's overall risk for CD is 5-10% (1/10 to 1/20). However, if the child has testing of the susceptibility genes, the risk will increase or decrease depending on the results.[1]

Individuals interested in learning about specific risks for themselves or family members should speak with their health care provider or a genetics professional.
Last updated: 2/5/2014

What are HLA-DQ2 and HLA-DQ8 with regard to celiac disease?

The HLA genes known to increase susceptibility to celiac disease are called HLA-DQA1 and HLA-DQB1. These genes provide directions for making proteins used by the immune system. They belong to a family of genes called the human leukocyte antigen (HLA) complex, which helps the immune system distinguish between proteins that belong in the body from those made by foreign invaders such as viruses and bacteria. The proteins made by these 2 genes attach to each other to form bigger proteins called heterodimers, which attach to proteins outside cells and help the body decide if they are foreign.[2] The heterodimers respond differently depending on the versions (alleles) of the HLA-DQA1 and HLA-DQB1 genes a person has.

Specific combinations of HLA-DQA1 and HLA-DQB1 gene alleles, called haplotypes, are associated with susceptibility to CD. The HLA-DQ2 haplotype results from certain HLA-DQA1 alleles, and the HLA-DQ8 haplotype results from certain HLA-DQB1 alleles.[1]

30% of the population has one of the CD-associated HLA alleles causing DQ2 and/or DQ8 susceptibility, but only 3% of people with one or both of these develop CD. Therefore, having these alleles does not mean a person has, or will have, CD. However, not having DQ2 and DQ8 susceptibility reduces a person's risk for CD to under 1% (less than 1 in 100).[2]

It is also known that:
  • People with only HLA-DQ8 are much less likely to have CD than those with only HLA-DQ2.
  • Among people with CD, there is no difference in severity of symptoms between people with only DQ2, or only HLA-DQ8.
  • People with both HLA-DQ2 and HLA-DQ8 do not appear to be at greater risk for CD than those who have only HLA-DQ2.
  • People with both HLA-DQ2 and HLA-DQ8 are more likely to have CD than those with only HLA-DQ8.[1]
Last updated: 2/7/2014

How are HLA-DQ2 and HLA-DQ8 celiac disease susceptibility inherited?

A person is considered to have HLA-DQ2 and/or HLA-DQ8 celiac disease susceptibility if they have a combination of particular versions (alleles) of the HLA-DQA1 and HLA-DQB1 genes, which are located on chromosome 6. These combinations are referred to as haplotypes.

The HLA-DQ2 celiac disease susceptibility haplotype can be inherited either in an autosomal dominant or autosomal recessive manner, depending on the specific alleles of these genes the parent has. HLA-DQ8 celiac disease susceptibility haplotype is inherited in an autosomal dominant manner.[1] However, even if a child inherits HLA-DQ2 and/or HLA-DQ8 celiac disease susceptibility, it does not mean the child will have celiac disease. Susceptibility to celiac disease can be inherited, but the disease itself is not inherited.

Each child of a person with HLA-DQ2 or HLA-DQ8 celiac disease-susceptibility haplotype has a 50% (1 in 2) chance to inherit each haplotype. However, the child of an affected person who has DQ2 celiac disease-susceptibility due to specific alleles on both copies of chromosome 6 (versus on 1 copy of chromosome 6) will definitely inherit one of the susceptibility haplotypes.[1] Genetic testing can show whether a person has the alleles on one chromosome or both chromosomes.

Because the genetics of celiac disease are complicated, individuals who have specific questions about their genetic test results, or risks to themselves and family members, should speak with a genetics professional.
Last updated: 2/7/2014

If 30% of the general population has a genetic susceptibility to celiac disease, why do only 3% of them develop celiac disease?

Only 3% of individuals with a known genetic susceptibility to celiac disease actually develop the disease because other factors play a significant role in the development of the condition. Environmental factors and changes in other genes (which are not yet well-understood) influence the development of this complex disease.[2]
Last updated: 2/7/2014

Can the inheritance of celiac disease be illustrated by a Punnett square?

A Punnett square is a diagram that may be used to find the chance to inherit a specific trait, when the genotype of both parents is known. It shows each possible combination of one maternal allele (version of a gene) with one paternal allele. However, Punnett squares are mainly used with traits that follow Mendelian inheritance; this means they are used for traits or conditions that are inherited in an autosomal dominant, autosomal recessive, X-linked dominant, or X-linked recessive manner.

Celiac disease is caused by the interaction of multiple genes, both with each other and with environmental factors. Celiac disease does not follow a simple Mendelian inheritance pattern, and therefore the inheritance cannot be illustrated by a Punnett square. Even though alleles that cause susceptibility to celiac disease are passed on in a Mendelian inheritance pattern, they are not enough to determine whether celiac disease will occur. In addition to environmental factors that contribute to celiac disease, other genes which are less well-understood are thought to play a role.

People who have specific questions about genetic risks for themselves or family members should speak with a genetics professional.
Last updated: 2/7/2014

Where can I learn more about the genetics of celiac disease?

You can learn more about the genetics of celiac disease by clicking on the following links. If you have questions regarding this information, it is recommended you review it with your health care provider or a genetics professional.
Last updated: 2/7/2014

How can I find a genetics professional in my area?

Genetics clinics are a source of information for individuals and families regarding genetic conditions, treatment, inheritance, and genetic risks to other family members. More information about genetic consultations is available from Genetics Home Reference. To find a genetics clinic, we recommend that you contact your primary healthcare provider for a referral.

The following online resources can help you find a genetics professional in your community:
Last updated: 6/5/2014

References
Other Names for this Disease
  • Celiac sprue
  • Coeliac disease
  • Gluten intolerance
  • Gluten-induced enteropathy
  • Gluten-sensitive enteropathy
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.