Genetics and Epigenetics in Diverticulitis: Can We Predict Disease?

Diverticular disease is common, but its clinical presentation and course from silent diverticulosis to diverticulitis or symptomatic diverticular disease remains unpredictable. Genetic studies have revealed a substantial heritable component, implicating extracellular matrix integrity, and neuromuscular function as key pathways. Large-scale genome-wide association studies have enabled the development of polygenic risk scores, which show promise for identifying individuals at increased risk, although their predictive advantage over demographic factors such as age and sex is modest. Increasing data provided by transcriptomic, epigenomic, and proteomic analyses will complement recent genetic discoveries, thereby providing an understanding of how gene regulation is affected by the environment. Integrating this emerging knowledge with microbiome studies and metabolomics could enable powerful, tailored “multiomic” prediction tools capable of delivering more accurate and clinically meaningful risk stratification.