Genome-Wide Analysis in Over 1 Million Individuals of European Ancestry Yields Improved Polygenic Risk Scores for Blood Pressure Traits Publisher Pubmed

Summary: In over 1M people, researchers found 113 new genetic links to blood pressure. Risk scores based on these genes may improve hypertension prediction. #Genomics #HeartHealth

Keaton JM^{1, 2} ; Kamali Z^{3, 4} ; Xie T³ ; Vaez A^{3, 4} ; Williams A¹ ; Goleva SB¹ ; Ani A^{3, 4} ; Evangelou E^{5, 6, 7} ; Hellwege JN^{8, 9, 10} ; Yengo L¹¹ ; Young WJ^{12, 13} ; Traylor M^{12, 14} ; Giri A^{2, 15} ; Zheng Z^{11, 16} Show All Authors
Source: Nature Genetics Published:2024

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 < 5 × 10−8) 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 = 2.22 × 10−126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 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 receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781–0.801) to 0.826 (95% CI, 0.817–0.836, ∆AUROC, 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. © The Author(s) 2024.