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

Hypertension affects >1 billion people worldwide. 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 >60% of SNP-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRS) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI=15.5-18.2 mmHg, p=2.22×10^-126) and more than a seven-fold higher odds of hypertension risk (OR=7.33; 95% CI=5.54-9.70; p=4.13×10^-44) in an independent dataset. Adding PRS into hypertension prediction models increased the area under the curve (AUC) from 0.791 (95% CI=0.781-0.801) to 0.826 (95% CI=0.817-0.836, ∆AUC=0.035, p=1.98×10^-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.