Steve Eyre from Manchester is giving tomorrow's IGM seminar at 1 PM about "RA - post GWAS.
I have been involved in researching the genetic susceptibility to rheumatoid arthritis (RA) since I joined the Arthritis Research Centre of Excellence, based at the University of Manchester, UK in 1996. Initially focussing on linkage studies using the large collection of family samples collected at the Centre as part of the National Repository, I quickly moved onto genome wide association studies (GWAS), as part of the Wellcome Trust Case Control Consortium (WTCCC), before leading on the fine-mapping of RA loci in the Immunochip study (Nature Genetics, 2012). This study used over 27,000 samples and led to the discovery of 14 new RA susceptibility loci. In recent years my lab has focussed on understanding the mechanisms by which these DNA variants lead to an increase risk of disease. In collaboration with Peter Fraser (Babraham, Cambridge) and Chris Wallace (University of Cambridge), my group has developed methods to interrogate the regions that are associated with RA, mainly regulatory enhancer regions, to determine the interacting gene targets. Using this Capture HiC methodology we are discovering how long range interactions, often involving multiple regions associated with different autoimmune diseases, regulate gene expression. In addition I have established collaborations with Soumya Raychaudhuri (Harvard Medical School, Boston), Caroline Ospelt (Zurich) and David Sansom (UCL), to look at the immunological, epigenetic and non-coding RNA consequences of the RA associated regions. These methods include ChIP, ATAC-Seq, RNA-seq and CRISPR genome editing.