Genetics of Inflammatory Bowel Disease-What is Unsought Goes Undetected

Inflammatory bowel disease (IBD) affects nearly 1% of North Americans and arises from complex interactions between genetics, environment, and the gut microbiome. This article examines IBD's genetic architecture-spanning monogenic, oligogenic, and polygenic disease-and highlights that genetic evaluation should not be limited by age. A negative genetic screen does not exclude a genetic basis for disease, as emerging mechanisms like mosaicism and regulatory variants may go undetected. The authors advocate for immunogenetic pathway-based classification to enable precision therapeutics, improve treatment outcomes, and reduce adverse effects, emphasizing that what is unsought in genetic testing will inevitably go undetected.