The impact of genetic risk loci on synovial fibroblast biology
Genetic factors contribute 50% to the risk of RA and the heritability of RA is estimated to be approximately 60%. Genome-wide association studies (GWAS) have identified over 100 genetic susceptibility loci for RA. However, only a small proportion of RA risk loci have been functionally analysed to date. In this project, we align genetic data with in depth analysis of the epigenetic landscape of synovial fibroblasts to determine which genetic risk loci lie within active, regulatory DNA regions in synovial fibroblasts, such as enhancers. We then modify these DNA regions in synovial fibroblasts by using the genome editing tools to see the molecular and functional impact of the genetic risk loci on fibroblast biology. Besides, we study the biology of synovial fibroblasts as well as analyse synovial tissues on a single cell level in patients with and without RA risk genetic variants.
Researcher in charge
- Prof Stephen Eyre, Arthritis Research UK Centre for Genetics and Genomics, University of Manchester, UK