Disentangling genetic effects on transcriptional and post-transcriptional gene regulation through integrating exon and intron expression QTLs

Expression quantitative trait loci (eQTL) studies typically consider exon expression of genes and discard intronic RNA sequencing reads despite their information on RNA metabolism. Here, we quantified genetic effects on exon and intron levels of genes and their ratio in lymphoblastoid cell lines, revealing thousands of cis-QTLs of each type. Genetic effects were often shared between cis-QTL types, but 6084 (41%) were not detectable at exon levels. We show that exon levels preferentially capture genetic effects on transcriptional regulation, while exon-intron-ratios better detect those on co- and post-transcriptional processes. Considering all cis-QTL types substantially increased the number of colocalizing GWAS variants (by 61%). It further allowed dissecting the potential gene regulatory processes underlying GWAS associations, suggesting comparable contributions by transcriptional (48%) and co- and post-transcriptional regulation (42%) to complex traits. Overall, integrating intronic RNA sequencing reads in eQTL studies expands our understanding of genetic effects on gene regulatory processes.