Fig. 5: Analysis of different MR methods on canonical causality and the causality between blood cell traits.

a The per locus detection rate (at P < 0.05) for phenotype combinations that are not considered causal or are unlikely to be considered causal by Morrison et al. b The per locus detection rate (at P > 0.05) for phenotypes that are considered causal. c Pleiotropic estimates (\({\hat{h}}_{{{{\bf{Y}}}}},\) where \({\hat{h}}_{{{{\bf{Y}}}}}\,\)P < 0.05) (y-axis) compared to MR-IVW absolute regional (\({\alpha }_{r}\)) estimate deviation from the meta-analyzed one (\(\bar{\alpha }\)) (x-axis). The r correlation coefficient is the Spearman correlation. The regression line is from linear regression n log₁₀ transformed comparisons. Due to a large number of points in the plot, the points are shown as a density. d Violin plot of the heterogeneity statistics of 306 complex trait to complex trait comparisons for the MR methods tested in this study. Upon meta-analysis of all the pairwise phenotype combinations in (a) and (b), we plot the Q statistic for each method (log₁₀ scale). The bars and whiskers in the plot refer to the minimum, median and maximum heterogeneity value. e Blood cell type and eQTL analysis results. MR-link-2 Bonferroni significant (P < \(5.15\cdot \,{10}^{-4}\)) causal links between cell type concentrations and the RNA expression of their respective marker genes (Supplementary Data 18). Green colored arrows indicate the cell type influences the RNA gene expression in blood causally. These are considered true causal links. The red arrows indicate an (incorrect) causal link between the gene expression and the blood cell type marker, indicating reverse causality. f Area under the receiver operator characteristic curve for the cell type directionality analysis for all MR methods tested in this study based on the reported P value of the method.