Defining Interactions Between the Genome, Epigenome, and the Environment in Inflammatory Bowel Disease: Progress and Prospects

Recent advances in our understanding of the pathogenesis of inflammatory bowel disease (IBD) have highlighted the complex interplay between the genome, the epigenome, and the environment. Despite the exciting advances in ge-nomics that have enabled the identification of over 200 susceptibility loci, these only account for a small propor-tion of the disease variance and the estimated heritability in IBD. It is likely that gene-environment (GxE) interactions contribute to missing heritability and these may act through epigenetic mechanisms. Several environmental factors, such as the microbiome, nutrition, and tobacco smoking, induce alterations in the epigenome of children and adults, which may impact disease susceptibility. Other mechanisms for GxE interactions are also directly perti-nent in early life. We discuss a model in which environ-mental factors imprint disease risk in a window of susceptibility during infancy that may contribute to later disease onset, whereas other elements of the exposome act later in life and contribute directly to the pathogenesis and course of the disease. Understanding the mechanisms un-derlying GxE interactions may provide the basis for new therapeutic targets or preventative strategies for IBD.

Automated summary

Recent advances in understanding the pathogenesis of IBD have shown the complex interplay between the genome, the epigenome, and the environment. Gene-environment interactions, especially through epigenetic mechanisms, may contribute to the missing heritability and alter disease susceptibility. Environmental factors, such as the microbiome, nutrition, and tobacco smoking, can induce changes in the epigenome that impact disease development. Understanding GxE interactions may lead to new therapeutic targets or preventative strategies for IBD.