The observation that GWAS variants associated with multiple distinct diseases within the same broader disease class (e.g., inflammation, cancer) repeatedly localize within the recognition sites of interacting transcription factors suggested that cohorts of such transcription factors might form shared regulatory architectures. To explore whether noncoding GWAS SNPs from related diseases perturb different recognition sequences of a common set of transcription factors, we tabulated all transcription factors for which at least 8 recognition sequences in DHSs were perturbed by GWAS SNPs associated with autoimmune diseases (Fig. 4A). Among the 22 factors identified were canonical immune signaling regulators, such as STAT1 and STAT3, NF-κB, and PPARα and PPARγ. These 22 transcription factors comprise a highly significant (P < 9.8 × 10-51, simulation vs. number of factors for random SNPs (12)), shared regulatory architecture that is repeatedly perturbed in a wide range of autoimmune disorders (Fig. 4A).
