Our genome contains vast networks that regulate the activity of protein-coding genes. Variations in this regulatory DNA (which does not encode proteins) may affect both when and how much of a given protein a cell produces. Disruptions in regulation can have a profound impact on healthy function – in fact, most genomic variants discovered by genome-wide association studies (GWAS), which identify variant locations within the genome associated with susceptibility to disease, are found in non-coding regions.
GWAS provides a good starting point for finding genetic associations with disease, but can implicate dozens or even hundreds of variants for every actual causal variant, so prioritizing them is essential. A team of researchers from The Jackson Laboratory (JAX), Benaroya Research Institute, and the Broad Institute of MIT and Harvard paired two high-throughput methods to examine GWAS-defined variants associated with five autoimmune diseases. In the process, they were able to zero in on non-coding variants associated with autoimmune disorders, one of which appears to play a key role in keeping the immune system’s T cells in check. Their findings appear in the journal Nature Genetics.
