In the last decades, thousands of common genetic variants have been associated with human diseases by genome-wide association studies (GWAS). However, the functional interpretation of GWAS hits is usually nontrivial, especially because most of them lay outside the coding genome. These noncoding variants presumably exert their effect by altering gene expression levels; therefore, expression quantitative trait loci (eQTL) mapping analyses represent an important step in understanding their functional relevance and identifying the target genes. Here we describe an alternative strategy for the detection of eQTL that takes into account the combined effect of genetic variants within regulatory regions and leverages the idea that changes in gene expression often are the consequence of the alteration of transcription factor (TF) binding.
Keywords: GWAS; Human genetic variants; Total binding affinity; Transcription factors; eQTL.