Inflammatory bowel disease should be classified into three distinct groups — ileal Crohn’s disease, colonic Crohn’s disease, and ulcerative colitis — the largest genotype-phenotype study of inflammatory bowel disease to date concludes.

The research involved nearly 30 000 patients with inflammatory bowel disease from 49 centres worldwide, as well as matching genotypes from more than 150000 variants.

Using the data to explore the genetic relationship between subtypes of inflammatory bowel disease with genetic risk scores the researchers discovered that ileal and colonic Crohn’s disease were at least as genetically distinct from each other as they were from ulcerative colitis.

They found that three loci (NOD2, MHC, and MST1 3p21) were associated with sub-phenotypes of inflammatory bowel disease, mainly disease location.

Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset.

The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease sub-phenotype, even after exclusion of NOD2, MHC, and 3p21.

Furthermore the risk score also identified a small number of patients with discrepant genetic risk profiles who were significantly more likely to have a revised diagnosis after follow-up.

The successful identification of genetic variants associated with complex diseases such as inflammatory bowel disease raises the exciting possibility of a more personalised approach to clinical management, the international team of researchers wrote in The Lancet.

They recommended that future translational and clinical research should move away from a binary classification of inflammatory bowel disease into ulcerative colitis and Crohn’s disease, instead considering ileal and colonic Crohn’s disease as separate disease entities.

Clinicians should also adopt the nomenclature in regular practice, they said.

Gastroenterologist Jane Andrews from the Royal Adelaide Hospital who was involved in the study said it was important clinicians looked carefully at whether their patients had Crohn’s disease affecting the colon or ileal Crohn’s disease.

“It sounds like it should be an easy thing to do but we know from a paper published recently that a lot of patients get misclassified,” she told the limbic.

Research by Professor Andrew’s group showed that while L2 classification signalling colonic disease alone was usually scored accurately, confusion and inconsistency existed when classifying patients into L1 (ileal disease alone) or L3 (ileal and colonic disease).

“At the moment people don’t stick to the small text in the classification system… this then gets in the way of teasing out these genetic signals and whether groups of patients respond better to a particular therapy,” she said.