Functional Fine-mapping of GWAS Variants for Complex Immune Traits


Thousands of genetic variants have been linked to common immune-mediated diseases, such as type 1 diabetes, rheumatoid arthritis, celiac disease and inflammatory bowel disease. However, the molecular mechanisms by which genetic variants predispose an individual to the development of an immune disease are largely unknown. Most of the disease variants localise in non-coding parts of the genome, indicating that they may function through regulation of gene expression. As gene expression can be highly cell type specific it is important that functional follow-up studies are carried out in disease most relevant cell types.  We have developed methods that integrate disease associated variants with histone marks to pinpoint critical disease cell types. One of the relevant cell types that we identified was the CD4 regulatory T cell (Tregs), a rare population of cells that suppress the immune response. Using Tregs from 100 healthy blood donors we generated detailed map of gene expression regulation by mapping quantitative trait loci (QTL) for RNA-seq (gene transcripts), ATAC-seq (chromatin accessibility) and ChIP-seq (promoter and enhancer histone modifications). We observed high co-localisation of immune disease GWAS signals with variants regulating expression of Treg specific genes. In my talk I will show how this approach allowed us to refine immune disease signals to functional variants and prioritise candidate causal genes for immune diseases.

Speaker's Profile:

Gosia graduated with a MSc from Jagiellonian University, Poland and a PhD (cum laude) from Groningen University, the Netherlands. She did her postdoc at Brigham and Women’s Hospital, Harvard Medical School and the Broad Institute. She is currently a Group Leader at the Sanger Institute, UK.