U.S. Department of Health and Human Services

New Genetic Variants for Celiac Disease

New Genetic Variants Associated with Celiac Disease Are Identified

Scientists have uncovered new genetic variants that are associated with the risk of celiac disease and have linked these variants to four pathways of the immune system. Celiac disease is a complex genetic disease that can cause damage to the intestine, resulting in poor absorption of nutrients, painful digestive and other symptoms, and other serious complications. These symptoms occur when people with the disease eat grains containing gluten--such as from wheat, rye, and barley--which provokes an abnormal immune response that attacks their intestine. For children, celiac disease can have devastating consequences, such as impaired growth and development, while adults may experience anemia, bone loss, and other complications. 

In an earlier study, scientists conducted a genome-wide association study (GWAS) to identify two gene variants that are required for celiac disease, and 12 chromosome regions that are associated with a risk for the disease. Although these findings were impressive, it was determined that all of the known variants did not account entirely for the genetic risk of celiac disease. In the new study, scientists set out to identify variants that may have smaller, yet critical, effects on disease risk. This was accomplished with a larger GWAS that included DNA samples from a larger number of patients with celiac disease and healthy volunteers. The samples were analyzed using a denser concentration of probes to identify differences in the DNA sequences of the patients compared with those of the volunteers. This approach was successful in uncovering 13 new chromosome regions that are associated with celiac disease and 13 additional chromosome regions with suggestive associations with celiac disease. Many of these regions were found to contain genes with functions related to the immune system. In addition, uncovering the genetic variants led the scientists to identify four specific immunological pathways that are relevant to the pathogenesis of celiac disease. The scientists also found that more than half of the variants associated with celiac disease correlate with the extent to which nearby genes are turned on or turned off (expressed), indicating that the variants may increase the risk of celiac disease by influencing the expression of other genes. These new findings have advanced knowledge of celiac disease and may also have important implications for other autoimmune diseases, such as type 1 diabetes.
 
Dubois PC, Trynka G, Franke L, et al. Multiple common variants for celiac disease influencing immune gene expression. Nat Genet 42: 295-302, 2010.