Book Section #18205

Abstract

Although it has been known for decades that susceptibility to inflammatory bowel disease (IBD) and its major subtypes is partly inherited, significant progress has been made in elucidating the genetic architecture of this disease only recently. The advent of genome-wide association studies (GWAS), together with the emergence of collaborative consortia, laid the foundation for extremely powerful genetic meta-analyses. This has led to crucial advances in the understanding of the pathophysiology of IBD, facilitating the identification of the underlying candidate pathogenic mechanisms. To date, approximately 250 IBD predisposing loci have been identified, indicating the immense complexity of the disease. The functional characterization of the genes mapping to these loci has particularly underscored the importance of immune system-related pathways in the development of IBD, showing a significant overlap of IBD with other immune-mediated disorders (IMDs) in the genetic architecture. However, despite the considerable advances in characterizing the genetic basis of this disease, aspects of the intricacy of IBD pathogenesis remain enigmatic and likely larger, as well as complementary data sets are required. In this chapter, we review the advancements in deciphering the genetic basis of IBD from candidate gene studies to GWAS and powerful meta-analyses and discuss the genetic overlaps of IBD with other IMDs. © Springer Nature Switzerland AG 2019.