Trans-eQTLs, where the SNP is located distal to the gene (>5 Mb) or on another chromosome, usually have smaller effect sizes than cis-eQTLs and thus require larger sample sizes for detection. However, trans-eQTLs could be relevant for complex traits because, compared to stronger cis-eQTL effects, each individual trans-effect is less likely to be dampened by compensatory post-transcriptional buffering or removed from the population by negative selection2,3. Indeed, genes regulated by weak eQTL effects are estimated to have more impact on the phenotype as compared to those regulated by strong eQTL effects4. Individual trans-eQTL SNPs can affect many genes and have a widespread impact on regulatory networks. Consequently, weak trans-eQTLs have the potential to identify trait-relevant genes1,5–10, and have already been used to prioritize genes that are likely to contribute to disease5.
