The article provides an overview of the genetic underpinnings of inflammatory bowel disease (IBD), focusing on the advancements in genotyping and sequencing technologies that have revolutionized our understanding of IBD. The authors highlight the identification of over 160 susceptibility loci for IBD, emphasizing the need to understand the fundamental functions of these alleles and their clinical relevance. They discuss the distinction between common and rare genetic variants, noting that rare variants often have more significant effects but are less penetrant. The article also explores the role of environmental factors, such as smoking and diet, in IBD pathogenesis and the complex interplay between genetics and the microbiome. Additionally, it reviews the use of advanced animal models, such as CRISPR-Cas9, to study the functional consequences of causative genes and the importance of cell type-specific approaches in IBD genetics. Finally, the authors discuss the potential clinical applications of IBD genetics, including diagnostic tools and predicting disease outcomes, while acknowledging the challenges in translating genetic findings into practical clinical use.The article provides an overview of the genetic underpinnings of inflammatory bowel disease (IBD), focusing on the advancements in genotyping and sequencing technologies that have revolutionized our understanding of IBD. The authors highlight the identification of over 160 susceptibility loci for IBD, emphasizing the need to understand the fundamental functions of these alleles and their clinical relevance. They discuss the distinction between common and rare genetic variants, noting that rare variants often have more significant effects but are less penetrant. The article also explores the role of environmental factors, such as smoking and diet, in IBD pathogenesis and the complex interplay between genetics and the microbiome. Additionally, it reviews the use of advanced animal models, such as CRISPR-Cas9, to study the functional consequences of causative genes and the importance of cell type-specific approaches in IBD genetics. Finally, the authors discuss the potential clinical applications of IBD genetics, including diagnostic tools and predicting disease outcomes, while acknowledging the challenges in translating genetic findings into practical clinical use.