Figure 1.

Schematic causal graphs used to illustrate (A) univariable Mendelian randomization (MR) analyses used in this study to estimate total effects between childhood body size and circulating metabolites, (B) multivariable MR analyses to estimate direct effects of childhood body size of circulating metabolites and (C) applying the same multivariable framework to estimate the indirect effects on circulating metabolites mediated along the causal pathway via adult body size. The highlighted arrows on these graphs illustrate the causal effect of childhood body size on the outcome being estimated in MR analyses. The textured arrows and grey shading indicate the effects that MR is typically robust to in comparison to observational analyses.