Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits.
Fiche du document
- doi: 10.1038/s41588-024-01714-w
- issn: 1061-4036
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41588-024-01714-w
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/38689001
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1546-1718
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_77928D3D34C18
info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/
Citer ce document
J.M. Keaton et al., « Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits. », Serveur académique Lausannois, ID : 10.1038/s41588-024-01714-w
Métriques
Partage / Export
Résumé
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.
