Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits

Abstract

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P<5x10(-8)) from the largest single-stage blood pressure (BP) genome-wide association study to date (n=1,028,980 European individuals). These associations explain more than 60 of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95 CI, 15.5-18.2 mmHg, P=2.22x10(-126)) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95 CI, 5.54-9.70; P=4.13x10(-44)) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95 CI, 0.781-0.801) to 0.826 (95 CI, 0.817-0.836, Delta AUROC, 0.035, P=1.98x10(-34)). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.