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

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Abstract

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.
Original languageEnglish
JournalNature Genetics
Publication statusAccepted/In press - 11 Mar 2024

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