We therefore analyzed monocyte expression data from 1,490 independent samples [45] and did not find evidence that this was a widespread phenomenon as we could replicate 46 out of the 130 different trans-eQTLs (each of these with a nominal p<1.0×10−5 in the monocyte data, Table S8). These replicated eQTLs include the genes AOAH, HBG2, GP9, F13A1, SAMD14, CD151, ITGA2B, MMRN1, THBS1, VWF and TPM1 mentioned above. Surprisingly we could also replicate the trans-eQTL effects on various blood-coagulation genes for mean platelet volume SNP rs12485738: One might argue that rs12485738 primarily increases platelet volume, resulting in a relatively higher volume of platelet-RNA when assessing total peripheral blood RNA. If this were to be the case, a measurable trans-effect is expected for platelet-specific (blood coagulation) genes in whole blood. Such an effect would then not actually be an expression-QTL, but rather a ‘cellular-QTL’. However, the trans-eQTLs for rs12485738 were also present in single cell-type monocyte datasets, indicating that the above concerns do not apply. Clearly, trans-eQTL effects can manifest themselves outside the primary cell-type, in which they are expected to operate.
