Fig. 1: PEAR1 alters plasma levels of SVEP1.
From: SVEP1 is an endogenous ligand for the orphan receptor PEAR1
a, b Schematic of SVEP1 (a) and PEAR1 (b) proteins. Domains were identified using the Simple Modular Architecture Research Tool (SMART)84. Teal, von Willebrand factor type A domain; purple, putative ephrin-receptor like; yellow, complement control protein/SUSHI repeat; orange, epidermal growth factor (EGF)-like domain or calcium-binding EGF-like domain or laminin-type EGF-like domain; scissors, putative cleavage site;55 P, representative phosphorylation of the PEAR1 intracellular domain. Protein coding variants discussed in the main text are denoted at the corresponding peptide. c Plasma SVEP1 (aptamer 11109.56.3) as a function of allelic copies of rs147639000 (PEAR1 p.D343N) in the INTERVAL study (N = 3,301). Beta = 0.67, P = 6.5 × 10−16. Boxes (c, d) depict upper and lower quartiles with median (center line); whiskers represent maximum and minimum values. (d) Plasma PEAR1 (aptamer 8275.31.3) as a function of allelic copies of rs147639000 (PEAR1 p.D343N) in the INTERVAL study (N = 3,301). Beta = −0.18, P = 0.03. e Manhattan plot of associations between PEAR1 D343N and 2,994 plasma proteins measured in INTERVAL. Each point represents the genomic location of the gene coding for a measured protein. f Two-sample MR of estimated SNP effects (with 95% confidence intervals) on PEAR1 in deCODE (x-axis) and either PEAR1, green, or SVEP1, blue, in INTERVAL (y-axis). The causal estimate is designated by a line of the corresponding color. PEAR1 Beta = 0.86, P = 2.4 × 10−37; SVEP1 Beta = −0.66, P = 3.5 × 10−20. g Two-sample MR of estimated SNP effects (with 95% confidence intervals) on SVEP1 in deCODE (x-axis) and either PEAR1, green, or SVEP1, blue, in INTERVAL (y-axis). The causal estimate is designated by a line of the corresponding color. PEAR1 Beta = −0.07, P = 0.002; SVEP1 Beta = 0.84, P = 2.5 × 10−54.
