A new study consisting of a large genetic and clinical data analysis provides insight into the variations of inflammatory bowel disease (IBD) and evidence that the classification into two disease groups — Crohn’s disease (CD) and ulcerative colitis (UC) — is overly simplistic. The article titled “Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: a genetic association study” was recently published in The Lancet journal.
IBD is a chronic, potentially life-threatening disease, caused by an exacerbated and inappropriate response of the immune system, leading to the inflammation and ulceration of the digestive tract. IBD is usually divided in its two main clinical manifestations: CD, which can affect any part of the gastrointestinal tract, and UC, where inflammation is restricted to the colon. A distinction between ileal and colonic CD has been previously suggested based on genetic differences, however the dual distinction of UC and CD is still the reigning dichotomy of IBD in clinical diagnosis, treatment decisions, and patient stratification for clinical trials.
Researchers studied the genetic profiles of 29,838 patients (16,902 with CD and 12,597 with UC), from 49 centers in 16 countries in Europe, North America, Australia, and Asia — the largest study of its kind. Scientists analyzed genetic and phenotipic associations, and generated genetic risk scores where a risk could be attributed to a particular type of IBD phenotype.
Results indicated that are three gene loci associated with the type of IBD, mainly in terms of location of the inflammation in the digestive tract. The genetic risk scores obtained also strongly distinguished colonic (large bowel) from ileal CD.
The large amount of data generated in this study provides evidence that there is a continuum of IBD disease that is not coherent with the dual categorization currently used, and that IBD is better interpreted in three groups (ileal CD, colonic CD, and ulcerative colitis). Moreover, interpretation of the data suggests that disease location is a major factor in disease behavior changes over time. The genetic overlap found between UC and CD explains the sometimes difficult disease-specific diagnosis, as only a small subset of genes are specific to one of the conditions.
“For a small subset of patients, genetics can uncover a misdiagnosis. Working with clinicians we hope this will help prevent costly and traumatic unnecessary surgery,” Dr. Jeffrey Barrett, the study’s corresponding author from the Wellcome Trust Sanger Institute and Director of the Centre for Therapeutic Target Validation, said in a news release.
However, he added, “in the vast majority of cases, the genetic scores we’ve identified for each condition are not different enough to be used diagnostically. Further research, pairing genetic data with patient responses to treatment over time will help us to better understand what’s happening on a molecular level in patients with different forms of IBD.”
Discovering genetic markers would be of great value in clinical diagnosis and treatment guidance, as genetic information informs disease biology and ultimately can lead to a more personalized treatment.
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