Figure 1.

ASE Test for Disease-Associated Variants

ASE that is shared among multiple individuals can indicate the presence of an eQTL (i.e., individuals with ASE are heterozygous for the common causal regulatory variant), multiple rare regulatory variants (i.e., each individual has a private variant impacting expression), or epigenetic effects where one haplotype is silenced relative to the other. We have developed a method that assesses enrichment of ASE effects for individuals harboring both the risk and the protective alleles (i.e., individuals who are heterozygous for the GWAS variant) as compared to homozygous individuals. Here, the expectation is that functional differences will be more manifest for individuals who possess both the risk and protective alleles for genes involved in the etiology of the trait. This enrichment is represented in the figure in that more ASE events are present in individuals heterozygous for the GWAS variant; green ratios describe the relative transcript abundance. This test complements eQTL approaches in that it can add support to the presence of an eQTL, as well as indicate an enrichment of other potential causal effects (independent of frequency) (i.e., rare or private variants) underlying the difference in risk and protective haplotypes.