Approved research

Elucidating the genetic architecture and shared origins of chronic inflammatory diseases

Lay summary

There has been a recent parallel 'epidemic' of asthma, allergy and other chronic inflammatory disorders, which might reflect shared genetic end gene-environment interactions. This seems particularly pronounced for childhood disorders. The aim of this project is to understand the shared mechanisms leading to asthma, eczema, and allergy as well as other inflammatory disorders in childhood, including recurrent infections, obesity, and neurological disorders/neurological development. Several susceptibility genes have been associated with chronic inflammatory diseases and verified in genome-wide association studies. However, these only explain a small proportion of disease variance observed between individuals. Increased efforts are required in order to understand the genetic involvement of the disease-causing mechanisms. Here we want to take several new approaches to identify susceptibility genes: One way to elucidate the pathobiology of a disease is to search for shared mechanisms among several similar diseases, which may improve the characterization of the individual diseases in the light of a combined disease map. Another approach is to focus on a well-defined homogenous subtype (such as the age of onset) of the disease and investigate the genetic make-up in this disease stratum. In this project, we will focus on childhood-onset of disease. Furthermore, we will apply novel methods to study interactions between genes, which has not yet been accounted for. Finally, we want to investigate how different subtypes are genetically and biologically related. We wish to leverage the large sample size and the many biological outcomes in UK biobank for this purpose. A better understanding of the shared genetic disease architectures along with a better characterization of disease subtypes might help to understand the cause of the parallel epidemic of inflammatory disorders in westernized countries and provide the basis for optimized treatment and preventive measures.