From the Guidelines
Yes, ulcerative colitis (UC) has a hereditary component.
Hereditary Risk Factors
- A family history of ulcerative colitis or Crohn’s disease increases the risk for developing ulcerative colitis 1.
- The risk of UC is greatest in first-degree relatives (incidence rate ratio 95% CI: 3.81–4.38), but is also raised in second-degree [IRR: 1.85; 95% CI: 1.60–2.13], and third-degree relatives [IRR: 1.51; 95% CI: 1.07–2.12] of UC patients, as well as in relatives of patients with Crohn’s disease although in a less pronounced fashion 1.
Interaction between Genetic and Environmental Factors
- UC is a lifelong disease arising from an interaction between genetic and environmental factors 2.
- The precise aetiology of UC is unknown, and therefore curative medical therapy is not yet available 2.
- Other factors such as appendicectomy for proven appendicitis before adulthood, and smoking may reduce the risk and severity of UC, while smoking cessation may predispose to ulcerative colitis 1.
From the Research
Ulcerative Colitis (UC) and Heredity
- Ulcerative colitis is considered to have a genetic component, with evidence suggesting that it is an inherited disorder in a proportion of cases 3.
- Studies have shown a pattern of familial aggregation, differences in prevalence among different ethnic groups, and a higher concordance rate in monozygotic twin pairs compared to dizygotic twin pairs, supporting the hypothesis of a genetic basis for UC 3.
- Genetic models suggest that UC is likely caused by one major gene, although the specific gene or genes remain to be identified 3.
Genetic Factors and UC
- Several genetic factors, including interleukin and interleukin receptor gene polymorphisms, play a central role in mediating and modulating inflammation in UC 4.
- Inflammation-related genetic polymorphisms are associated with an increased risk of developing UC, and understanding these genetic factors is important for clinical utility and validity 4.
- A study found that genetic susceptibility to UC, estimated by polygenic risk scores, was associated with an increased risk of developing the disease, and that a healthy lifestyle can reduce this risk 5.
Genetic Architecture of UC
- A recent study found that the genetic architecture of UC is similar across East Asian and European ancestries, but with some ancestry-dependent differences in genetic effects 6.
- The study identified 80 UC loci in East Asian individuals and 320 when meta-analyzed with European individuals, including 81 new loci 6.
- The findings highlight the importance of diversity in understanding the genetic basis of UC and improving the accuracy of polygenic risk scores 6.