Genetic Factors

Genetic Factors

Evidence to suggest that genetic factors contribute to susceptibility to IBD comes from:

  • Twin studies
  • Ethnic studies
  • Familial aggregation
  • The discovery of IBD susceptibility genes

Twin studies

  • Monozygotic twins with Crohn’s disease have a much higher disease concordance (37%) than dizygotic twins (7%)
  • For ulcerative colitis, the concordance rates are less (10 vs. 3% for monozygotic and dizygotic twins, respectively), suggesting a less important genetic impact, in comparison with Crohn’s disease

Ethnic studies

  • Highest rates in Whites, lower rates in Black Americans and the lowest rates in Asians.
  • The prevalence of disease is much higher in the Jewish population than any other ethnic group
  • Ashkenazi Jews carry the highest risk, with an age-corrected risk for IBD of 8.9% for the offspring of patients with IBD

Familial aggregation

  • Increased risk among relatives with IBD (Offspring 2 parents with IBD > offspring 1 parent with IBD > sibling > 2nd-degree relative)

The discovery of IBD susceptibility genes

  • One way of trying to understand why some individuals develop disease and other’s do not, is to conduct a genome-wide association study
  • This technique basically involves gathering, and comparing, genetic markers (or SNPs) (genetic blueprint contained within a cell) of two groups of individuals, one group with the disease of interest, and one without. If genetic variations are more frequent in people with the disease, the variations are said to be “associated” with the disease
  • Over 70 of these genetic markers have been identified in both Crohn’s disease and ulcerative colitis populations

On a technical note – Susceptibility Genes

In Crohn’s disease

  • Genetic research indicates an association between disease susceptibility and specific chromosomes (the building blocks of cells), specifically 16q2 (named IBD1), 12q (IBD2), 6p (IBD3), and 10
  • Genetic research has identified a NOD2 (nucleotide oligomerization domain) gene (recently renamed CARD15). This discovery provided support for the long-held hypothesis that Crohn’s disease results from a genetically dysregulated host immune response to luminal bacteria
  • The regions around genetic markers (SNPs) identified as associated with Crohn’s disease have been progressively explored with the discovery of a handful of other causitive genes defining new mechanisms and understanding of IBD.

In ulcerative colitis

  • Ulcerative colitis tends to run in families, suggesting that genetics have a role in this disease
  • About 10 to 25 percent of people with ulcerative colitis have a first-degree relative (either a sibling or parent) with inflammatory bowel disease (either ulcerative colitis or Crohn’s disease)
  • Genetic research has identified an association of ulcerative colitis with the DR2 allele