Genome-wide pleiotropy analysis identifies novel blood pressure variants and improves its polygenic risk scores

Abstract

Systolic and diastolic blood pressure (S/DBP) are highly correlated modifiable risk factors for cardiovascular disease (CVD). We report here a bidirectional Mendelian Randomization (MR) and pleiotropy analysis of systolic and diastolic blood pressure (BP) summary statistics from the UKB-ICBP BP genome-wide association study (GWAS) and construct a composite genetic risk score (GRS) by including pleiotropic variants. The composite GRS captures greater (1.11-3.26 fold) heritability for BP traits and increases (1.09- and 2.01-fold) Nagelkerkes R2 for hypertension (HTN) and cardiovascular disease (CVD). We replicated 118 novel BP pleiotropic variants including 18 novel BP loci using summary statistics from the Million Veteran Program (MVP) study. An additional 219 novel BP signals and 40 novel loci were identified after meta-analysis of the UKB-ICBP and MVP summary statistics but without further independent replication. Our study provides further insight into BP regulation and provides a novel way to construct a GRS by including pleiotropic variants for other complex diseases.