Compared to the gene expression from bulk tissues, scRNA-seq datasets are less affected by cell-type composition and serve as the best current source for replicating, prioritizing and annotating trans-eQTLs. While we have compiled, to our knowledge, the largest available blood scRNA replication dataset, it was still only 3.6% of the sample size of the discovery study. It is therefore unsurprising that only 35 trans-eQTLs reached the significance threshold (FDR<0.05). None-the-less, 84% of the 729 trans-eQTLs attaining nominal significance (P<0.05) also showed allelic concordance with the discovery analysis, suggesting that there are intracellular effects among our trans-eQTLs, even if case-by-case distinction of cell-type-composition and intracellular effects is not yet possible. Upcoming large-scale single cell eQTL studies53 (e.g. https://www.eqtlgen.org/single-cell.html), as well as highly-powered eQTL analyses in non-blood tissues54 and cell lines, will be instrumental in distinguishing intracellular effects from cell-type composition.
