Genetic studies in immune-mediated diseases have yielded a large number of disease-associated loci. Here we review the progress being made in 12 such diseases, for which 199 independently associated non-HLA loci have been identified by genome-wide association studies since 2007. It is striking that many of the loci are not unique to a single disease but shared between different immune-mediated diseases. The challenge now is to understand how the unique and shared genetic factors can provide insight into the underlying disease biology. We annotated disease-associated variants using the Encyclopedia of DNA Elements (ENCODE) database and demonstrate that, of the predisposing disease variants, the majority have the potential to be regulatory. We also demonstrate that many of these variants affect the expression of nearby genes. Furthermore, we summarize results from the Immunochip, a custom array, which allows a detailed comparison between five of the diseases that have so far been analyzed using this platform.