study 27 we do not find an enrichment of genetic correlations unequal to zero (data not shown) which could be expected given our high degree of tissue-independency of cis-effects from our cis-eQTL mapping approach. However, as our sample size is limited measurement error in genetic covariance cannot be ruled out.The finding that the majority (>60%) of the genetic effect of expression traits is regulated by components other than those acting in cis, points to the need for studies of the trans-regulatory landscape. Trans-regulatory variants are known to have small effect sizes and thus have previously been difficult to map given limited sample sizes and lack of appropriate replication studies 4. However, the recent findings of disease related trans-variants regulating the expression of multiple genes are promising 28,29. A dilemma with genome-wide eQTL analysis is that only a small proportion of the variants survive multiple testing corrections and by restricting to signals based solely on arbitrary cut-offs, many true hits are likely to be missed. This can be circumvented by analytic methods such as studying the global effect of trans-variants using proportion of true positives (π1) as presented here. By applying this approach and with thorough replication we found evidence of
