that common SNPs may in some instances tag low frequency variants 25,26 we expect that a subset of the missing cis-heritability still will be accounted for by low frequency and rare variants supporting large-scale exome and genome re-sequencing initiatives for complex trait mapping. The missing cis-heritability has also intriguing implications for GWA signals in cases where the effect of the lead SNP is mediated via a cis-eQTL, i.e. if a known GWA variant is an eQTL and therefore affects disease risk by modulating expression of a gene, then any additional rare variant modulating expression of the same gene in the same tissue should also affect the same trait. This leads us to predict that on average an additional 40% or more of signal remains to be discovered at cis-eQTL GWAS loci (of which we identify 358 in this study). These estimates are based on calculations within each tissue and thus do not represent tissue-independent cis-heritability. In agreement with a previous 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
