Celiac disease

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.

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]

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.

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]

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.

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.

• Celiac disease. Genetics Home Reference. October, 2011
• Alessio Fasano. Genetics of Celiac Disease. Medscape Reference. June 21, 2012.
• Cara L Snyder, Danielle O Young, Peter HR Green, and Annette K Taylor. Celiac Disease. GeneReviews. July 3, 2008.
• Genetic Testing. The University of Chicago Celiac Disease Center.

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.