The trans- analysis for the breast cancer risk loci support the assertion that some risk alleles act through TFs that, in turn, influence their target genes. The data demonstrate that target genes of a TF can be used as a surrogate readout for TF activity as has been shown in a recent study (Small et al., 2011). For example, 8q24 associated target genes are enriched for the MYC motif providing an additional layer of support that MYC is a common upstream TF. In addition to MYC, we discovered that the 6q25 and 9q31 risk loci act through the ESR1 and KLF4 TFs. Since the TFs themselves were not associated with genotypic status using an eQTL-based method, we turned to measuring allelic expression of the TFs.
