Genetic variAtioN anD Altered Leukocyte Function in health and disease (GANDALF) – molecular mechanisms underlying non-coding locus associations

Genetic studies have found many regions in our DNA that contribute to autoimmune disease. A lot of these regions function in CD4 T cells. CD4 T cells are a type of white blood cell called a lymphocyte that serve an important role in your immune system by helping defend the body against infection. Exactly how tiny changes in CD4 T cell DNA leads to disease, however, is largely unknown.

In our last study, we looked at DNA changes at 13 regions linked to autoimmune diseases. Donors who carried one copy of the risk variant and one copy of the non-risk variant provided samples. Using these, we found out how risk variants affect CD4 T cells. This helped us uncover a protective pathway that is disrupted in multiple diseases. Our experiments provide data across the whole genome (not just the 13 regions). If we knew whether the donors had any risk variants at other disease regions, we could then use our data for future studies. This has two knock-on effects. First, it means we can study other risk variants without needing more samples. Second, it speeds up our efforts to find new disease pathways. This maximises the value of our data. It also help us find new drug targets faster. This is why we have asked for more genetic data from the donors who helped with our previous study. We will not be able to identify the donors from the provided data as it has been fully anonymised.