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DOP021. Familial risk of inflammatory bowel disease: a population-based cohort study 1977–2011

F. Trier Moller1,2, V. Andersen3, T. Jess2, 1Southern University of Denmark, Institute for Regional Health Research, Odense, Denmark, 2Statens Serum Institut, Department of Epidemiology Research, Copenhagen, Denmark, 3Southern University of Denmark, Institute for Regional Health Research - SHS, Odense, Denmark

Background

The inflammatory bowel diseases (IBD) - ulcerative colitis (UC) and Crohn's disease (CD) - are caused by complex gene–environment interactions. This study provides updated familial aggregation patterns in a large population-based Danish IBD cohort.

Methods

Our cohort study was based on the entire Danish population during 1977–2011 (n = 8,410,048). Through a unique personal identification number assigned to each Danish citizen, sex, date and location of birth, identity of parents, and information on vital status and emigration were available. This information was used to establish kinship in the entire population. Individuals receiving a diagnosis of IBD during the time period (n = 69,915) were identified using the Danish National Registry of Patients. Risk of IBD in family members to individuals with IBD was assessed by Poisson regression analysis.

Results

The risk of CD was 8-fold increased in 1. degree relatives to at least two individuals with IBD, 4.6-fold increased in 1. degree relatives to one family member with CD, and even 3-fold increased if the 1. degree relative had UC (Table 1). The same pattern was observed for the risk of UC (Table 2). Second-degree relatives to patients with CD or UC were also at significantly increased risk not only of the same but also the other subtype of IBD, whereas the risk of IBD was less pronounced in third degree relatives to individuals with IBD.

Figure: Rate ratio of contracting CD when having a family member with either CD or UC, as compared to having a family member of the same type without CD (black line). Notice the axis change in the twin figure reflecting the substantially increased rate ratio among twins.

Table 1. Rate ratio RR (95% CI) of contracting CD in family members to an IBD affected case, as compared to having a relative of the same type without a diagnosis of IBD.
Type of exposure/type of relativeRR (95% CI)
1. degree relative2. degree relative3. degree relative
Two or more relatives with CD or UC8.48 (6.72, 10.7)2.89 (2.06, 4.05)1.33 (0.50, 3.55)
One CD relative4.57 (4.12, 5.06)1.86 (1.57, 2.22)1.95 (1.48, 2.57)
One UC relative2.87 (2.66, 3.11)1.53 (1.35, 1.73)1.12 (0.84, 1.50)
Table 2. Rate ratio RR (95% CI) of contracting UC in family members to an IBD affected case, as compared to having a relative of the same type without a diagnosis of IBD.
Type of exposure/type of relativeRR (95% CI)
1. degree relative2. degree relative3. degree relative
Two or more relatives with CD or UC5.98 (4.99, 7.17)2.10 (1.52, 2.91)1.20 (0.50, 2.88)
One CD relative2.19 (1.99, 2.42)1.34 (1.15, 1.56)1.25 (0.93, 1.67)
One UC relative3.04 (2.89, 3.20)1.49 (1.35, 1.64)1.39 (1.11, 1.73)

Conclusion

This large-scale population-based study provides updated numbers of familial aggregation of IBD. Familial exposure to CD not only increases the risk of CD but also of UC markedly and vice versa, and the ratio rises with closer familial ties and in families with multiple affected members.