More Crohn's Disease Genes Discovered by CHOP Researchers

Published on in CHOP News

December 15, 2010 — Researchers at The Children’s Hospital of Philadelphia contributed important pediatric data to the largest-ever genetic study of Crohn’s disease. In this study, the International IBD Genetic Consortium drew on samples from more than 22,000 patients and 29,000 controls from around the world.

About inflammatory bowel disease

A chronic, painful inflammation of the digestive tract, inflammatory bowel disease (IBD) includes Crohn’s disease (affecting any part of the digestive tract) and ulcerative colitis (limited to the large intestine). It affects some 2 million U.S. children and adults.

An abnormal overreaction in the body’s immune system is believed to trigger the inflammation in IBD. Like many common disorders, IBD has complex causes, resulting from any of a number of genes that may interact with each other and with environmental factors.  

About the study

Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics; Kai Wang, PhD, also from that Center; and Robert N. Baldassano, MD, director of the Center for Pediatric Inflammatory Bowel Disease, were co-authors of the current paper, and have collaborated previously with each other on genetic studies of pediatric IBD. The current study appeared online Nov. 21, 2010 in Nature; the study leader was Miles Parkes from the University of Cambridge in the UK.

Study findings

The international study consortium identified 30 new locations at which gene variants were associated with a higher risk of having Crohn’s disease. When added to previous studies, a total of 71 gene variants have now been discovered, and the total is expected to grow in the future. Currently, more genes have been linked to Crohn’s disease than to any other disease.

Because the gene variants found in this study are believed not to directly cause IBD, but instead act as signposts to other gene variants more directly involved in causation, further studies are needed to identify causative genes and understand their biological functions. However, many of the candidate genes affect signaling within the immune system and regulate immune responses. Many of the gene locations found in the current study have previously been linked to other autoimmune diseases such as asthma, celiac diseases, type 1 diabetes and rheumatoid arthritis. 

Genetics play a larger role in children with IBD

The CHOP researchers contributed genotype data from more than 1,600 pediatric patients with Crohn’s disease and 4,000 controls to the discovery set of the study. When combined with data from adult-onset cases, the joint analysis identified 31 new genetic variants linked to IBD. Hakonarson said that genetics tends to play a stronger role in children with IBD than adults with the disease.

“In childhood-onset IBD, genetic factors play a stronger role and hence there is early onset of the disease,” Hakonarson said. "In adult-onset IBD, by contrast, there is a longer period of time for non-genetic effects, such as infections and dietary factors and their interactions, as well as exposures to medications and various environmental toxins to come into play to trigger the disease in subjects who may have weaker genetic susceptibility and hence a later disease onset.”

Baldassano added: “Our goal is to use better understanding of how specific genes contribute to IBD to develop more appropriate and effective treatments for the disease. Ultimately, personalized medicine will help us to select the best treatment for each patient, based on the patient’s genetic profile.”

Related information

Visit the Center for Pediatric Inflammatory Bowel Disease


John Ascenzi, Department of Public Relations, 267-426-6092,