U.S. Department of Health and Human Services

Genetics of Inflammatory Bowel Disease in Children

Genetic Risk Factors Associated with Inflammatory Bowel Diseases (IBD) in Children

Researchers have identified five new genetic variations that predispose children to developing IBD. The two major forms of IBD—Crohn’s disease and ulcerative colitis—are marked by chronic and destructive inflammation in the intestinal tract. While the precise causes of IBD are unknown, there is a strong genetic component that predisposes individuals to developing these diseases. Previously, nearly 50 genetic risk factors had been identified as associated with IBD. Many of these genetic factors involved components of the immune system that control intestinal inflammation. These risk factors, however, were typically identified in adults with IBD. Since some clinical aspects of IBD in children differ from those in adults, it was important to extend these studies to identify genetic risk factors associated with the development of IBD in pediatric populations. 

An international team of researchers has carried out the largest genome-wide association study (GWAS) to date for identifying genetic variants associated with IBD in children. In a GWAS, scientists scan thousands of genomes for genetic variants that are more common in individuals with a disease—such as a form of IBD—than in healthy individuals. In this study, comparing children with IBD and healthy children, the researchers identified variants in five new regions of the genome that increase children’s risk of developing IBD. One of the most prominent risk factors identified for Crohn’s disease was found near the IL27 gene. This gene codes for a protein that is involved in an immune response previously implicated in the pathogenesis of Crohn’s disease. The researchers showed that colon cells from children with Crohn’s disease had much lower levels of IL27 gene activity than cells from healthy individuals, suggesting that the risk variant reduces the amount of protein made from the IL27 gene. In addition to the five new genetic regions, the pediatric population also has many of the genetic risk factors previously identified in adults with Crohn’s disease or ulcerative colitis. This implies that these forms of IBD involve similar biological pathways in adults and children, but that IBD which develops in children may involve some distinct pathways as well. Defining the genetic variations that predispose individuals to developing IBD enables researchers to gain insight into the causes of these diseases and potentially develop strategies to help detect, treat, and prevent early-onset IBD in children.​

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Imielinkski M, Baldassano RN, Griffiths A, et al. Common Variants at Five New Loci Associated with Early-Onset Inflammatory Bowel Disease. Nat Genet 41: 1335-1340, 2009.