Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits.
Details
Serval ID
serval:BIB_77928D3D34C1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits.
Journal
Nature genetics
Working group(s)
Million Veteran Program, Lifelines Cohort Study, CHARGE consortium, ICBP Consortium
Contributor(s)
van Duijn C.M., Butterworth A.S., Vaez A., Teumer A., Johnson A.D., Morris A.D., Peters A., Goel A., Campbell A., Keavney B.D., Hayward C., Newton-Cheh C., Nelson C.P., Chasman D.I., Levy D., Ruggiero D., de Geus E., Hofer E., Zeggini E., Boerwinkle E., Girotto G., Warren H.R., Watkins H., Kolcic I., Jukema J.W., Hui J., Howson JMM, Sundström J., Chambers J.C., Danesh J.N., Risch L., Caulfield M.J., Laakso M., Tobin M.D., De Borst M.H., Waldenberger M., Samani N.J., Melander O., Raitakari O.T., Polašek O., Munroe P.B., Ridker P.M., van der Harst P., Elosua R., Ripatti S., Lehtimäki T., Young W.J., Kamali Z., Kutalik Z.
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
05/2024
Peer-reviewed
Oui
Volume
56
Number
5
Pages
778-791
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
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 <sup>-8</sup> ) 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 <sup>-126</sup> ) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10 <sup>-44</sup> ) 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 <sup>-34</sup> ). 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.
Keywords
Humans, Genome-Wide Association Study, Multifactorial Inheritance/genetics, Blood Pressure/genetics, White People/genetics, Polymorphism, Single Nucleotide, Hypertension/genetics, Genetic Predisposition to Disease, Risk Factors, Male, Female, Genetic Risk Score
Pubmed
Web of science
Open Access
Yes
Create date
03/05/2024 15:12
Last modification date
27/09/2024 16:45