Document Type

Article

Publication Date

3-1-2022

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 horizontal pleiotropy analysis of S/DBP summary statistics from the UK Biobank (UKB)-International Consortium for Blood Pressure (ICBP) (UKB-ICBP) BP genome-wide association study 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) Nagelkerke's R2 for hypertension and CVD. We replicated 118 novel BP horizontal 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 a 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.

Publication Source (Journal or Book title)

Genetic Epidemiology

First Page

105

Last Page

121

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