A complementary method of identifying cis- regulated genes is allelic imbalance (AI). AI for a given gene can be measured when an individual is heterozygous for a transcribed polymorphism. Significant deviations in from a 1:1 ratio in RNA levels indicate genetic and/or epigenetic cis- influences on a gene (Babak et al., 2010; Campino et al., 2008; Ge et al., 2009; Heap et al., 2010). Recently released TCGA RNA-sequencing data enables evaluation of AI in tumor samples (Methods). The expectation is that individuals who are heterozygous for the functional regulatory polymorphism (or any variant in linkage disequilibrium with it) will display AI in the target gene while homozygous individuals will demonstrate less AI (Forton et al., 2007; Lefebvre et al., 2012)(Figure S3, related to Figure 2 and 3).
