Proper Use of Allele-Specific Expression Improves Statistical Power for cis -eQTL Mapping with RNA-Seq Data

At present, high-throughput RNA sequencing (RNA-seq) is rapidly replacing expression microarrays to assess gene expression abundance. Unlike microarrays that only measure the total expression of each gene, RNA-seq also provides information on allele-specific expression (ASE), which can be used to distinguish cis- eQTLs from trans- eQTLs and, more importantly, enhance cis- eQTL mapping.

However, assessing the cis -effect of a candidate eQTL on a gene requires knowledge of the haplotypes connecting the candidate eQTL and the gene, which can not be inferred with certainty. The existing two-stage approach that first phases the candidate eQTL against the gene and then treats the inferred phase as observed in the association analysis tends to attenuate the estimated cis -effect and reduce the power for detecting a cis -eQTL.