Although putative biological mechanisms of action could be assigned to half of the identified trans-eQTLs, significant replication in scRNA-seq, purified cell type and cell line datasets was very limited. Such low replication rates suggest two likely causes. First, a number of the distal effects are likely driven by inter-individual cell-type-composition differences, which occur in any bulk tissue. While such effects could be informative in the context of some complex traits (i.e. for autoimmune diseases), the most interesting information lies in the intracellular effects. Furthermore, while we corrected for unknown confounders in our analyses, some residual cell-composition effects remain in the data. Therefore, it was not possible to reliably distinguish cell-type-dependent effects from intracellular ones. Instead, our results should serve as a prioritized list for in-depth functional studies.
