Applying ‘omics to understand and predict juvenile arthritis and its associated uveitis (360G-Wellcome-211030_Z_18_Z)

Juvenile idiopathic arthritis (JIA) is the most common rheumatological condition of childhood. Significant numbers of JIA patients (up to 30%) develop complications with their eyes (uveitis, JIA-U) and are at risk of blindness. We do not know why uveitis is so common in JIA, why only some children get uveitis or what causes more severe disease. Current research suggests our genes and our environment are involved but their exact contributions are unclear. This project will look at how genes related to similar autoimmune conditions may be involved in JIA and systematically assesses the evidence for environmental factors associated with JIA and JIA-U. This project will then look for genes specifically associated with JIA-U in a genome-wide association study. However, we know from similar diseases that having predisposing genes is insufficient alone to cause disease. Epigenetics studies how genes are switched on/off (our "epigenome") and helps explain how genes and the environment act together to cause disease. Thus, this project will also examine whether the epigenome mediates JIA and JIA-U disease risk. Finally, all of this information will be used to identify key elements of the epigenome of JIA patients and test whether changes to these can predict development of JIA-U.