Fig. 2: The developed IL6 genetic instrument is associated with measurable reductions in serum CRP mainly by influencing IL6 expression and circulating IL-6 levels.
From: IL6 genetic perturbation mimicking IL-6 inhibition is associated with lower cardiometabolic risk
a, The effects of the 12-variant IL6 genetic score versus a previously described 26-variant IL6R genetic score15,17,20 on reductions in CRP levels across percentiles. The bars represent the percentage reduction in median CRP levels across different genetic score percentiles. b, The effect estimates of genetic variants comprising the IL6 instrument on IL6 expression across immune cells, other cell types or lines and tissues, as extracted from the eQTL catalog resource35—blue boxes indicate nominally significant (two-sided P < 0.05) effects on expression. c, The association of genetically proxied downregulation of IL-6 signaling through the IL6 12-variant, as captured by decreases in serum log-transformed CRP (x axis) with circulating IL-6 levels (scaled in s.d. units, y axis) on IVW MR analysis. The blue line shows the regression slope with the overall association (two-sided P = 5 × 10−7). Each point represents the effect estimates for a genetic variant, with horizontal and vertical error bars indicating the 95% CIs for CRP and IL-6 reductions, respectively. CRP associations are derived from the UK Biobank (N = 464,264), IL-6 associations are derived from ref. 36 (N = 74,679). DLPFC, dorsolateral prefrontal cortex; iPS cells, induced pluripotent stem cells; LCL, lymphoblastoid cell line.
