IBD: a family affair

doi:10.1016/j.bpg.2003.12.006

Best Practice & Research Clinical Gastroenterology

Volume 18, Issue 3, June 2004, Pages 525-539

https://doi.org/10.1016/j.bpg.2003.12.006 Get rights and content

Abstract

The recent molecular advances in the understanding of the genetics of inflammatory bowel disease (IBD) have their grounding in studies examining IBD within different family groups and populations. The risk of IBD is highest in first-degree relatives of an IBD proband but more distant relatives are also at increased risk. The risk is higher for relatives of a CD proband. The risks of developing IBD for ‘high-risk’ relatives might be as great as 1 in 3 but in general first-degree relatives have a 1 in 10–20 risk. Three recent systematic studies have identified a total of 326 European twin pairs to examine disease concordance rates. The derived heritability in Crohn's disease is greater than for many complex diseases and is currently under detailed examination. Strong concordance has been shown, in particular for disease type and disease location, in multiplex families and twin studies. More than 75% children are diagnosed with IBD at a younger age than their parents but true genetic anticipation appears unlikely.

Section snippets

Assessing Risk for relatives

The greatest risk factor for the development of inflammatory bowel disease (IBD) is having an affected family member.¹ First-degree relatives, especially siblings, are at greatest risk but the risk also extends to more distant relatives. Quantification of this risk depends on a combination of ethnicity, the type of IBD—Crohn's disease (CD) or ulcerative colitis (UC)—and the exact relationship between the person at risk and the proband. Each of these risk factors will be examined in detail to

Risk of IBD in first-degree relatives—siblings, parents and offspring

The first-degree relatives of a patient with IBD have been studied, collectively and individually, more than other relatives. Studies have consisted mainly of selected hospital populations but a few have covered whole populations. In each study the risk of CD and UC has been considered separately for each relative and some studies have given a relative risk of CD/UC/IBD compared to the population studies. Table 1 highlights the results from studies looking at CD and Table 2 for UC.

In these

Familial phenotypes

The phenotypic similarity or difference between family members with IBD has been compared in familial against sporadic disease and in multiplex family studies. The difficulty in comparing many of the studies is that no standard definition of phenotype was agreed upon when the studies were performed. The adoption of the Vienna classification as a standard for CD phenotyping has the advantage of setting a phenotypic benchmark.³¹ Unfortunately, almost all of the studies were performed before this

Anticipation

The term ‘anticipation’ describes a genetic phenomenon in which disease severity increases and age of onset decreases in subsequent generations affected by the disease in question. Anticipation has been demonstrated in a range of monogenic neurological disorders including Huntingdon's chorea, Friedrich's ataxia, fragile X syndrome and myotonic dystrophy.⁴⁰ The common mechanism unifying these diseases is expansion of nucleotide triplet repeats, with the more repeats that are present the earlier

Twin studies

Twin studies have been a powerful tool in the identification of the different contributions of genes and environment to IBD disease aetiology. In general, twins are brought up in the same environment so differences in disease prevalence between monozygotic and dizygotic pairs are used to estimate the genetic contribution to a disease. Thus, the question in IBD is: ‘What are the relative contributions to CD and UC from twin studies and how do these compare to other diseases?’

The early IBD

Genetic counselling

Despite many family studies, translating the study results into clinically relevant data that patients understand remains a great challenge. Genetic counselling, if available, seems to be welcomed by most patients.⁵⁷ The known and unknown relative risks for CD and UC are summarised in Table 7, Table 8.

Even when adjusted, these relative risks are still fairly imprecise and difficult to apply outside the population they were derived from. If they are to be used at all, recent information on the

Summary

It is clear, from family studies, that the risk of IBD is significantly higher in family members. Twins are the highest risk group, followed by first-degree relatives. Both these groups are at increased risk of both IBD types, the risk being greater for developing the same type of IBD as the affected proband. Concordance for some features of disease phenotype has been shown in both groups. Relatives of a CD proband are at an increased risk of IBD in all studies. The risk of IBD in second- and

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6IBD: a family affair

Abstract

Section snippets

Assessing Risk for relatives

Risk of IBD in first-degree relatives—siblings, parents and offspring

Familial phenotypes

Anticipation

Twin studies

Genetic counselling

Summary

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

American Journal of Gastroenterology

Gastroenterology

Gastroenterology

Digestive and Liver Disease

Gastroenterology

American Journal of Gastroenterology

American Journal of Gastroenterology

Gastroenterology

American Journal of Gastroenterology

Gastroenterology

Gastroenterology

American Journal of Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Lancet

American Journal of Gastroenterology

Lancet

American Journal of Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

American Journal of Gastroenterology

Prevalence of inflammatory bowel disease among relatives of patients with Crohn's disease

Scandinavian Journal of Gastroenterology

6
IBD: a family affair