Translating IBD Genomics into Clinical Practice

Rapid advances in genomics have transformed our understanding of the biological mechanisms underlying inflammatory bowel disease (IBD). Although adult-onset IBD is predominantly polygenic, current applications of genetics lie in monogenic forms of IBD and pharmacogenetics. This review aims to serve as a primer for clinicians and outline the evolving role of genomics in IBD, identify clinical scenarios in which genetic testing is relevant, and highlight its implications for diagnosis and treatment.

A narrative review of the literature was performed, focusing on monogenic causes of IBD, diagnostic approaches to suspected monogenic cases, therapeutic implications and established pharmacogenetic associations relevant to clinical practice.

Genome-wide association studies have identified more than 320 susceptibility loci associated with Crohn's disease and ulcerative colitis, implicating pathways involving innate immunity, autophagy, epithelial barrier integrity, and cytokine signalling. However, these common variants individually confer modest disease risk and explain only a limited proportion of heritability, restricting their direct clinical utility. In contrast, nextgeneration sequencing has enabled the identification of rare, high-penetrance monogenic defects, particularly in very-early-onset and treatment-refractory IBD. Recognition of these disorders has important therapeutic implications, including targeted biologic therapy and, in selected cases, curative hematopoietic stem cell transplantation. In parallel, pharmacogenetic testing, most notably for NUDT15 and TPMT variants, has become integral to optimising thiopurine safety.

Advances in genomics are steadily reshaping the clinical management of inflammatory bowel disease. Integration of genetic testing, particularly in patients with very early-onset or difficult-to-treat disease and in optimising drug safety, can support more informed, individualised treatment decisions. As genomic technologies become increasingly accessible, their incorporation into routine IBD care has the potential to improve outcomes and move clinical practice closer towards personalised medicine.