To further assess the contribution of different classes of GRS in the final score, we constructed two metaGRSs: (i) a score based on stroke-related GRSs (AS, IS, CES, LAS, SVS) and CAD-related GRSs (46K, FDR202, 1KGCAD) but no other risk factors; and (ii) a metaGRS based on stroke-related GRSs (AS, IS, CES, LAS, SVS) and risk-factor-related GRSs (SBP, DBP, TC, LDL, HDL, TG, AF, BMI, Height, T2D, Smoking) but no CAD-related GRSs (Supplementary Fig. 6). Addition of either risk-factor GRSs or CAD-related GRSs each led to more powerful metaGRSs compared with the IS-only GRS, but the best score was achieved when combining both types of GRS into the 19-component metaGRS, indicating that both types of GRS had independent information about stroke risk. Note that due to pleiotropy there is some overlap between the genetic signal for CAD and risk factors such as BP and cholesterol.
