The genetics of Crohn's disease

Abstract

This chapter summarises progress in understanding the genetic basis of Crohn's disease (CD). It starts with a brief review of family studies for CD epidemiology and then summarises findings of the so-called "linkage era". Given the success of genome-wide association studies (GWAS) in terms of identifying CD susceptibility loci, the focus of this chapter is on the key GWAS studies and their main results. These have demonstrated association with multiple Th17 pathway components and strongly implicated defects in innate immunity, particularly in autophagy and the handling of intracellular bacteria, as playing key roles in CD pathogenesis. Besides GWAS for adult-onset CD, paediatric-onset GWAS are discussed. Although paediatric-onset CD presents with more extensive disease and rapid progression compared to adult-onset CD, genetic studies have shown marked molecular similarities between the two disease forms. Not only have single GWAS contributed to completing the molecular map of CD genetics, but also systematic cross-phenotype analyses and meta-analyses of several CD GWAS, both of which are discussed in the current chapter. Lastly, the first sequencing studies for CD as well as future challenges are described.