Fig. 2. Non-linear Mendelian Randomization: causal associations between iron status biomarkers and all-cause mortality.

Dose-response curves (black) between iron traits and all-cause mortality in HUNT (gray lines give 95% confidence interval). The x-axis gives a: serum iron levels (µmol/L) [N = 56,654], b: serum ferritin (µg L⁻¹) [N = 2335], c: transferrin saturation (%) [N = 56,651] and d: total iron-binding capacity (TIBC) (µmol L⁻¹) [N = 56,654]. The y-axis gives the hazard ratios for all-cause mortality with respect to the reference values (red dot), which represent the established target values (iron, TIBC, TSP)⁸⁴ or median value (ferritin) for the traits. The curve gradients represent the localized average causal effect at each point. N = sample size.