Supplementary Figure 4: Pleiotropic effect of the KLKB1 locus.

(a), Trans-pQTL effect detected at four independent SNPs at the KLKB1 locus with multiple trans-regulated proteins associated with a missense SNP (rs3733402) and neighboring SNPs. The assessed allele is given in brackets. The associations of the SNP and proteins are presented as a bar plot. The y axis refers to the association strength in terms of –log P value. Association direction is shown. A blue positive bar indicates that the allele assessed is associated with a higher level of the protein. A red negative bar indicates association to a lower level. (b), Inter-correlation structure of nine proteins trans-regulated by rs3733402. Colored circles represent Spearman correlation coefficients: positive correlation (blue) and negative correlation (red). Color intensity and circle size indicate correlation strength. (c), Association of the KLKB1 locus in cis and in trans: trans-pQTL SNPs located at the KLKB1 locus are depicted as red diamonds; the corresponding trans-regulated proteins are depicted as blue ellipses; cis-pQTL SNPs regulating these proteins are shown as green diamonds; complex diseases and traits associated with SNPs and genes are shown as gray rectangles. We also show expression QTLs (eQTLs) on the same plot: genes whose expression is regulated in cis by trans-pQTL SNPs are depicted as pink ellipses. Blue edges correspond to trans-pQTLs, green edges to cis-pQTLs, red edges to cis-eQTLs and gray edges to trait associations.