title: Digesting the genetics of inflammatory bowel disease: insights from studies of autophagy risk genes.
abstract: The success of genetic analyses identifying multiple loci associated with inflammatory bowel disease (IBD) susceptibility has resulted in the identification of several risk genes linked to a common cellular process called autophagy. Autophagy is a process involving the encapsulation of cytosolic cellular components in double-membrane vesicles, their subsequent lysosomal degradation, and recycling of the degraded components for use by the cell. It plays an important part in the innate immune response to a variety of intracellular pathogens, and it is this component of autophagy that appears to be defective in IBD. This has lead to the hypothesis that Crohn's disease may result from an impaired antibacterial response, which leads to ineffective control of bacterial infection, dysbiosis of the intestinal microbiota, and chronic inflammation. Several recurrent themes have surfaced from studies examining the function of autophagy-related genes in the context of IBD, with cellular context, disease status, risk variant effect, and risk gene interplay all affecting the interpretation of these studies. The identification of autophagy as a major risk pathway in IBD is a significant step forward and may lead to pathway-focused therapy in the future; however, there is more to understand in order to unravel the complexity of this disease.
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
authors.forename: Amrita
authors.initials: A
authors.lastname: Kabi
authors.forename: Kourtney P
authors.initials: KP
authors.lastname: Nickerson
authors.forename: Craig R
authors.initials: CR
authors.lastname: Homer
authors.forename: Christine
authors.initials: C
authors.lastname: McDonald
mesh_terms: D001343:Autophagy / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D010588:Phagosomes / Q000235:genetics*; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics; D012306:Risk
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D018167:Receptors, Calcitriol; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D019204:GTP-Binding Proteins; C513539:IRGM protein, human