String-database network connections between proximal cis-gene and target plasma protein.

<p>All short String paths that connect proximal cis-genes with the target plasma protein are shown. The colour intensity of each gene shows the eQTL association-strength with the index-SNP. The nodes highlighted with bold border show paths that satisfy P<0.05 in network permutation analysis. A) the rs61598054-SNP is harboured in an intron of the <i>LACE1</i> gene, but have no paths to the target gene <i>NGF</i> and a more likely mechanism is therefore <i>FOXO3</i> -> <i>AKT1</i> -> <i>NGF</i>, which involves a rs61598054-trans-eQTL effect on <i>AKT1</i>. In permutation analysis of re-wired networks this is stronger than 95% of random networks. B) Similarly for rs693918, while located between <i>SRD5A2</i> and <i>MEMO1</i>, the path <i>XDH</i> -> <i>TLR4</i> -> <i>IL18</i> is a more likely mechanistic path, supported by eQTL effects on both <i>XDH</i> and <i>TLR4</i>. C) The rs61598054-<i>AKT1</i> trans-eQTL from panel A in 235 IFN-stimulated monocytes and the rs10947260-ATF3 trans-eQTL from panel D in 89 mammary artery samples. D) Example of ambiguous findings regarding the rs10947260 -> -> -> IL6: The SNP has a coding-proxy in <i>BTNL2</i>, literature mining evidence for the <i>AGER</i> gene, but also eQTL-weighted pathway evidence for both <i>ATF6B</i> and <i>NOTCH4</i>.