Detecting shared pathogenesis from the shared genetics of immune-related diseases

Genetic factors play an important part in the development of autoimmune and inflammatory disorders, such as rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, asthma and coeliac disease. An increase in co-morbidity and clustering of different autoimmune diseases in families suggest the existence of an overlap in the genetic background of these diseases.Until recently, only the human leukocyte antigen (HLA) locus and a few candidate genes have consistently been associated with these immune-related diseases. However, with the development of Genome-wide association (GWA) studies, dozens of new susceptibilty genes and loci have been identified in various immune-related diseases.Many of these newly identified loci are shared by two or more immune-related diseases, and the majority of these shared genes belong to just a few immunological pathways: T-cell signalling and differentiation, innate immunity, and tumour necrosis factor (TNF) signalling. Moreover, many of the disease-specific associated genes are involved in the same pathways.Many immune-related diseases are characterized by high numbers of T cells, as well as by an imbalance in T-cell subsets. The association of T-cell differentiation pathway genes with multiple immune-related diseases suggests that the functional roles of the T helper (TH) 1, TH17 and T regulatory (Treg) molecules in these diseases are altered by genetic factors.Association of autoimmune diseases with genes that are involved in innate immunity provides links to bacterial and viral infections as the triggers of disease and might lead to the development of new tools for prevention, such as vaccines.Understanding the shared pathogenesis between immune-related diseases might provide targets for therapeutic intervention. Targeting pathways rather than genes and correlating the genetic profile of a patient to the effectiveness of a specific therapy might open new avenues in clinical trials.So far, the genetic study of immune-related diseases has only revealed the tip of the iceberg, as more genes need to be found and the true causal variants need to be identified.The notion of shared genetic pathways identifies new and powerful approaches for determining the full repertoire of susceptibility genes — instead of focusing on single diseases, genetic resources can be shared.