Sunday, December 23, 2012

IBD and Genetics


Will my relatives get IBD?


Genetics is believed to play a definitive role in the risk of developing Crohn’s Disease and Ulcerative Colitis.  One of the most common questions in IBD from the relatives of those diagnoses is what their likelihood of developing the disease is going to be.  Risk can be either vertical (the risk of children of IBD sufferers contracting the disease) or horizontal (the risk of siblings developing the disease).  Both vertical and horizontal risks have been shown to be higher than the general population risk.

Determining the role of genetics and inheritance in the likelihood of developing a particular disease generally involves twin studies.  Identical twins, who share the same genetics*, are compared to fraternal twins, who share the same parents but come from different eggs.  Because twins are generally raised in the same circumstances and exposed to the same environmental factors, differences in the rate of occurrence between identical and fraternal twins can show the degree of genetic influence on disease development.  In the rare cases where twins are separated and raised in different environments, further confirmation or disconfirmation of a genetic link can be made.  If twins living in different locations and raised by different parents have the same predisposition to developing a particular disease as twins raised together, the genetic link is that much stronger.  Because of the rarity of IBD, twin studies are difficult to perform, especially separated twin studies.

The largest twin study to-date on Crohn’s and UC was done in Sweden in the 1980’s.  The study found a stark difference between the two diseases.  When one twin has UC, the other twin is not significantly more likely than the general population to develop UC.  When a twin has Crohn’s, however, the other twin is twice as likely as the general population to develop the disease.  Additionally, if an identical twin has Crohn’s, the other twin has a greater than 50% chance of developing Crohn’s, showing a strong genetic link.  In a follow-up study fifteen years later, additional UC diagnosis showed an 18% chance of a second twin developing UC if the first twin had it.  (1), (2)

What about the non-twin factors in inheritance?  Familial incidence is the single biggest risk factor identified in the likelihood of being diagnosed with IBD.  In a study of 1,000 patients, 87 were found to have first degree relatives with Crohn’s disease – primarily siblings.(3)  The likelihood of a sibling developing IBD if another sibling is diagnosed is between 10 and 20%, significantly higher than the population as a whole. (4).  The evidence additionally suggests a stronger maternal influence on whether or not IBD is developed in children.  (5)

What if you are looking to have kids?  The risk of a child developing IBD is 3–10% when one parent has IBD and 30–50% if both parents have the IBD.  Predictive genetic testing is, unfortunately, still in its infancy and not an accurate predictor (alone) of developing IBD.  (6,7)

Despite the definitive role of genetics in IBD, research is currently trying to understand what specific genetic markers are predictive.  Additionally, there is almost certainly a non-genetic environmental factor or factors at play that has yet to be identified (though there are several well-grounded possibilities).

Bottom Line

  • IBD has a definite genetic component (but it is not believed to be exclusively genetic). 
  • Siblings of those with IBD have a 10 – 20% chance of developing the disease.
  • Children of parents with IBD have a 3 – 10% chance of developing the disease.  If both parents have IBD, the risk rises to 30-50%. 


* Technically, genetic mutations can occur even with identical twins.  Additionally, epigenetic factors can strongly influence identical twin development.  That said, identical twins still share a genetic makeup that is substantially more alike than other categories of relatives.

1.       C Tysk, E Lindberg, G Järnerot, and B Flodérus-Myrhed.  Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking.  Gut, 1988.
2.       Halfvarson J, Bodin L, Tysk C, Lindberg E, Järnerot G.  Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics.  Gut, 2003.
3.       Freeman, Hugh J. M.D.  Familial Crohn's Disease in Single or Multiple First-Degree Relatives. Journal of Clinical Gastroenterology.  2002. 
4.       R.K Russell, MBChB, MRCP(Ed), MRCPCH, J Satsangi, BSc, MBBS, Dphil, FRCP(Ed).  IBD: a family affair.  Best Practice and Research:  Clinical Gastroenterology.  2004.
5.       Zuzana Zelinkova, Pieter C. Stokkers, Klaas van der Linde, Ernst J. Kuipers, Maikel P. Peppelenbosch, Christine P.J. van der Woude.  Maternal imprinting and female predominance in familial Crohn's disease.  Journal of Crohn’s and Colitis.  2011.
6.       Satsangi, J., Grootscholten, C., Holt, H., & Jewell, D. P.. Clinical patterns of Familial Inflammatory Bowel Disease. Gut, 1996.
7.       Shelly A. Cummings  and David T. Rubin.  The Complexity and Challenges of Genetic Counseling and Testing for Inflammatory Bowel Disease.  Journal of Genetic Counseling, 2006.

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