  Genetic variation affecting gene regulation is a central driver of phenotypic
differences between individuals and can be used to uncover how biological
processes are organized in a cell. Although detecting cis-eQTLs is now routine,
trans-eQTLs have proven more challenging to find due to the modest variance
explained and the multiple tests burden of testing millions of SNPs for
association to thousands of transcripts. Here, we successfully map trans-eQTLs
with the complementary approach of looking for SNPs associated to the
expression of multiple genes simultaneously. We find 732 trans- eQTLs that
replicate across two continental populations; each trans-eQTL controls large
groups of target transcripts (regulons), which are part of interacting networks
controlled by transcription factors. We are thus able to uncover co-regulated
gene sets and begin describing the cell circuitry of gene regulation.
