The same analysis in the context of 17 different malignancies exposed a very different network of transcription factors connecting seemingly disparate cancer types (P < 7.1 × 10-11, simulation (12)) including neoplastic regulatory relationships, linking FOXA1 and breast cancer, FOX03 and colorectal cancer, and TP53 and melanoma, breast and prostate cancer (Fig. 4B). We also analyzed six neuropsychiatric disorders, and identified 23 transcription factors whose recognition sequences were perturbed by at least 3 disease-associated variants (fig. S13). Collectively, these results support the hypothesis that shared genetic liability may underlie many related categories of disease (24, 25).
