Most studies prioritizing genes for complex traits have considered only cis-eQTL effects and our blood cis-eQTLs can be used for that purpose. However, cis-eQTL effects have been estimated to contribute to a limited fraction of the heritability of gene expression, while the combination of many weak trans-eQTL effects is estimated to explain the majority51, emphasizing the importance of distal effects. At the same time, the interpretation of trans-eQTLs in blood remains challenging: limited replication and the influence of blood-cell-composition suggest that the effects are highly cell-type-specific. Nevertheless, the replication analyses we carried out in PBMC scRNAs-seq data prioritized 729 trans-eQTLs, and half of the identified trans-eQTLs were assigned to a putative biological mechanism of action, with transcriptional regulation through TF activity being the most prevalent.
