Fig. 2: Polygenic score (PGS) associations with circulating proteins.
A Volcano plot of PGST2D_gw-protein beta coefficients (obtained from linear regression) and the unadjusted -log10 p-values (two-sided), with the colour indicating the magnitude of the -log10 p-values. Labelled proteins are among the top 1% in terms of variance (R2) explained by the PGST2D_gw. B Beta-beta plot of PGST2D_gw beta coefficients on circulating proteins with (y-axis) and without (x-axis) BMI adjustment. The diagonal is dashed grey, while the regression line is solid grey. Each point represents a protein; light blue points indicate replicated proteins that remained significant with the adjustment, red points indicate replicated proteins that were no longer significant after the adjustment, and dark blue points indicate proteins that did not significantly replicate prior to adjusting for BMI or pQTLs. C Pearson’s correlations of PGS beta coefficients from the regression on circulating protein levels. Red indicates pairs of PGS with positively correlated effect sizes; blue indicates negatively correlated effect sizes. “*” indicates correlations with a p-value < 0.05 and “**” indicates correlations with a p-value < 0.001 (a Bonferroni correction for 45 comparisons). P-values are unadjusted and two-sided t test as the test statistic follows a t distribution. D Bar plot indicating the overlap between proteins significantly associated with the T2D PGS and the other cardiometabolic PGS. The x-axis is the PGS label, and the y-axis is the percentage of PGST2D_gw-associated proteins that are also associated with another PGS (e.g., over 60% of proteins were also associated with the PGSBMI). E Beta-beta plot of PGST2D_gw effect sizes on circulating proteins with (y-axis) and without (x-axis) pQTL adjustment, with the same definitions as panel (B) albeit for a pQTL adjustment.
