Fig. 4: Drug response phenotype associations with polygenic risk scores (PRS).

a Drug response associations with PRS calculated for the absolute (post-base) and logarithmic relative (log(post)-log(base)) biomarker difference colour-coded by the drug (blue: statins, orange: metformin, green: antihypertensives, purple: beta blockers). Standardized effect sizes (biomarker/PRS effect) correspond to an SD change for 1SD increase in PRS. A negative sign means that increased PRS increases treatment efficacy (i.e., larger biomarker difference compared to low PRS). All associations are adjusted for sex, age and drug-specific covariates. The center of the error bars corresponds to the linear regression association estimate, and the error bars represent the 95% confidence intervals calculated in each drug response cohort (sample sizes in Supplementary Data 4). LDL cholesterol (LDL-C); total cholesterol (TC); HDL cholesterol (HDL-C); systolic blood pressure (SBP); heart rate (HR); ACE-inhibitor (ACEi); calcium channel blocker (CCB). b Statin users stratified by 1) LDL-C baseline levels adjusted for LDL-C PRS and 2) LDL-C PRS quintiles with each tile showing the average LDL-C biomarker response (top: absolute, bottom: relative difference). Darker blue values correspond to stronger biomarker reductions. c Statin users stratified by 1) LDL-C baseline levels, 2) LDL-C PRS and 3) rs7412 genotype (individuals with the TT genotype are omitted as their sample size was too low). Boxes bound the 25th, 50th (median, centre), and the 75th quantile of LDL-C post-treatment measures. Whiskers range from minima (Q1 - 1.5*IQR) to maxima (Q3 + 1.5*IQR) with points above or below representing potential outliers. Numerical values and sample sizes in each stratum are shown in Supplementary Data 18.