Monlong, J. et al. Nat. Commun. 5, 4698 (2014).

Expression quantitative trait loci (eQTL) methods are used to associate genetic variants with changes in gene expression. Although RNA sequencing can measure the expression of individual splice forms, existing tools do not describe the abundance of individual isoforms relative to expression of the entire gene. Monlong et al. introduce sQTLseekeR, statistical software that represents splice forms as multivariate isoform ratios to detect splicing QTLs (sQTLs), genetic variants that are associated with altered splicing ratios. In analyzing 465 lymphoblastoid cell lines with genotype data from the 1000 Genomes Project and RNA sequence data from the GEUVADIS project, sQTLseekeR identified over 1,900 sQTLs (at a 1% false discovery rate), including a handful of 'trans' sQTLs that affect the splicing of multiple genes and are enriched for RNA processing and splicing genes.