Although low frequency/rare cis-variants seem to contribute significantly to the total heritable cis-effect , as discussed above, a large proportion of the total heritability (>60%) of gene expression is still unexplained, indicating that the effect of trans-regulatory variants on gene expression are likely to be critical to inter-individual differences in gene expression. We thus proceeded to explore the trans-regulatory landscape across tissues. Given the large number of tests performed and the relatively small effect sizes of trans-eQTLs we chose the P< 5×10−8 GWAS threshold (corresponding to FDR less than 10%) to select possible candidates for further investigation including replication analysis in independent samples (see below). At P< 5×10−8 we found 639, 557, and 609 trans-eQTLs in adipose, LCL and skin respectively (Supplementary Table 8). The relative proportion of trans-eQTLs per tissue is the inverse of that seen in the cis-eQTL analysis, perhaps reflecting the different external environments present for complex tissues vs. cultured cells. In contrast to the cis results, nearly all trans-eQTLs seem to be tissue-dependent, have relatively small effect sizes and are associated with transcripts with lower average h2 (h2adipose=0.19, h2LCL=0.18 and h2skin=0.13).
