Abstract
Systolic and diastolic blood pressure (S/DBP) are highly correlated and modifiable risk factors for cardiovascular disease (CVD). We report here a bidirectional Mendelian Randomization (MR) and GWAS pleiotropy analysis of S/DBP summary statistics from large published BP GWAS and construct a composite genetic risk score (GRS), capturing respectively 21%, 11%, and 227% more of SBP, DBP and PP heritability than achieved with the traditional GRS. The composite GRS improves the prediction of hypertension and CVD in persons of European as well as African and Asian descent. We identified and confirmed 120 novel BP pleiotropic variants that are not in linkage disequilibrium with known variants, including 17 novel BP loci. We further observed significant age-modulated genetic effects on BP, hypertension and CVD in both Europeans and Asians. Our study provides further insight into BP regulation and provides a novel way to construct a GRS for correlated traits.