Orofacial granulomatosis (OFG) is a rare inflammatory condition characterized by the presence of granulomas in the oral and facial regions and is often associated with intestinal Crohn’s disease (CD). Thanks to GWAS studies the genetics of CD is quite well defined but we know much less about the causes of OFG. Over recent years we have sought to understand this better and see if the overlap between the two conditions can be explained in part by similar genetic causes. We now have evidence suggesting this may indeed be the case for some key genes (e.g. NOD2) that we have shown are involved in both CD and OFG. We wish to explore this further to help understand the route to pathogenesis in OFG and develop tools to identify those patients who might be at high risk of developing CD.
The aim of this projects will be to investigate the genetic causes of OFG through whole exome sequencing, determine the genetic overlap with CD and explore the role of disease-causing variants that are identified particularly with a focus on NOD2 pathway and atopy. We will also measure the microbiome using biological markers in the blood and saliva of individuals in our study and apply modelling techniques to help us investigate their interactions with the microbes in the mouth and gut and correlate this with immune status and genetics.
Year 1: sample analysis and sequencing
Year 2: data acquisition, validation, microbiome analysis
Year 3: final analysis and modelling, functional studies