cis-eQTLs are all in strong linkage disequilibrium with the SNPs Kwan et al described (IRF5: rs7808907 and rs6969930: D' = 1, R2 = 0.74 rs2863095, MRPL43: rs2863095 and rs12241232: D' = 0.89, R2 = 0.75, PTER: rs7909832 and rs1055340: D' = 1, R2 = 1), supporting our observations. Kwan et al examined different exonic effects through an independent validation using quantitative RT-PCR (out of a total of 25 validated genes) and estimated that only 39% of the detected cis-eQTLs influence overall gene expression levels. For the remaining cis-eQTLs genetic variation results in preliminary terminated transcripts (18%), not initiated transcripts (11%), transcripts that are spliced differentially (26%) or a combination of these (6%). We acknowledge that our use of oligonucleotide arrays, predominantly targeting the 3' end of genes, gives a more limited picture of splicing since only 3' termination events can be seen. However, the data presented above and alluded to by Kwan et al [39] suggest that SNP genotypes can have a significant effect on alternatively spliced transcript isoforms. This additional layer of complexity should be examined in future genetical genomics experiments to fully elucidate the genotypic effects on RNA.
