Gastroenterology

Gastroenterology

Volume 144, Issue 4, April 2013, Pages 736-742.e1
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Heritability and Familial Aggregation of Diverticular Disease: A Population-Based Study of Twins and Siblings

https://doi.org/10.1053/j.gastro.2012.12.030Get rights and content

Background & Aims

Little is known about the role of heritable factors in diverticular disease. We evaluated the contribution of heritable factors to the development of diverticular disease diagnosed at a hospitalization or outpatient visit.

Methods

Using nationwide patient registries, we identified 142,123 incident cases of diverticular disease diagnosed at a hospitalization (1977–2011) or an outpatient hospital visit (1995–2011) in Denmark, including cases in 10,420 index siblings and 923 twins. We calculated standardized incidence ratios for siblings versus the general population and concordance rates for monozygotic versus dizygotic twin pairs as measures of relative risk (RR).

Results

The RR for diverticular disease in siblings of index cases was 2.92 (95% confidence interval [CI], 2.50–3.39) compared with the general population. The RRs were similar irrespective of the sex of the sibling or index case and were particularly strong in siblings of hospitalized cases and cases that underwent surgery. The proband-wise concordance rate for monozygotic twins was double that of dizygotic twins (0.16 [95% CI, 0.11–0.22] vs 0.07 [95% CI, 0.05−0.11], respectively). The RR of diverticular disease in one twin when the other had diverticular disease was 14.5 (95% CI, 8.9–23) for monozygotic twins compared with 5.5 (95% CI, 3.3–8.6) for dizygotic twins. Associations were stronger in female monozygotic twins compared with male twins (tetrachoric correlation, 0.60 [95% CI, 0.49−0.70] vs 0.33 [95% CI, 0.13−0.51]; P = .03 in an analysis stratified by sex and zygosity). We estimate that 53% (95% CI, 45%–61%) of susceptibility to diverticular disease results from genetic factors.

Conclusions

Based on a population-based study in Denmark, genetic factors appear to contribute to development of diverticular disease.

Section snippets

Subjects and Methods

We studied familial aggregation of diverticular disease, including diverticular complications and asymptomatic diverticulosis in siblings, and in a separate analysis compared the phenotypic similarity of monozygotic and dizygotic twins and estimated the heritability of diverticular disease.

Descriptive Data

We identified 142,123 incident cases with diverticular disease recorded at a hospitalization from 1977 to 2011 or an outpatient hospital visit from 1995 to 2011 in Denmark. Of these, 13,268 were born after 1952, 10,586 had an identifiable mother in the Civil Registration System, and 10,420 were index cases with a total of 16,374 siblings. We followed up the siblings for a total of 79,241 person-years. The overall population incidence of a hospital admission or visit for diverticular disease in

Discussion

In this nationwide population-based study, we found strong evidence for a heritable contribution to the etiology of diverticular disease. Siblings of index cases were 3 times more likely to develop diverticular disease than the general population, and measures of twin similarity were consistently higher for monozygotic twin pairs than for dizygotic twin pairs. The RRs were greater among siblings of cases who were hospitalized or had surgery associated with a diagnosis of diverticular disease.

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    This article has an accompanying continuing medical education activity on page e14. Learning Objective: Upon completion of this CME activity, successful learners will be able to explain the role for genetic factors in diverticular disease.

    Conflicts of interest The authors disclose no conflicts.

    Funding Supported by the Clinical Epidemiology Research Foundation, Aarhus University Hospital, Denmark.

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