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Lookup NU author(s): Valentina Mamasoula
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024. The Author(s). 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.
Author(s): Keaton JM, Kamali Z, Xie T, Vaez A, Williams A, Goleva SB, Ani A, Evangelou E, Hellwege JN, Yengo L, Young WJ, Traylor M, Giri A, Zheng Z, Zeng J, Chasman DI, Morris AP, Caulfield MJ, Hwang S-J, Kooner JS, Conen D, Attia JR, Morrison AC, Loos RJF, Kristiansson K, Schmidt R, Hicks AA, Pramstaller PP, Nelson CP, Samani NJ, Risch L, Gyllensten U, Melander O, Riese H, Wilson JF, Campbell H, Rich SS, Psaty BM, Lu Y, Rotter JI, Guo X, Rice KM, Vollenweider P, Sundstrom J, Langenberg C, Tobin MD, Giedraitis V, Luan J, Tuomilehto J, Kutalik Z, Ripatti S, Salomaa V, Girotto G, Trompet S, Jukema JW, van der Harst P, Ridker PM, Giulianini F, Vitart V, Goel A, Watkins H, Harris SE, Deary IJ, van der Most PJ, Oldehinkel AJ, Keavney BD, Hayward C, Campbell A, Boehnke M, Scott LJ, Boutin T, Mamasoula C, Jarvelin M-R, Peters A, Gieger C, Lakatta EG, Cucca F, Hui J, Knekt P, Enroth S, De Borst MH, Polasek O, Concas MP, Catamo E, Cocca M, Li-Gao R, Hofer E, Schmidt H, Spedicati B, Waldenberger M, Strachan DP, Laan M, Teumer A, Dorr M, Gudnason V, Cook JP, Ruggiero D, Kolcic I, Boerwinkle E, Traglia M, Lehtimaki T, Raitakari OT, Johnson AD, Newton-Cheh C, Brown MJ, Dominiczak AF, Sever PJ, Poulter N, Chambers JC, Elosua R, Siscovick D, Esko T, Metspalu A, Strawbridge RJ, Laakso M, Hamsten A, Hottenga J-J, de Geus E, Morris AD, Palmer CNA, Nolte IM, Milaneschi Y, Marten J, Wright A, Zeggini E, Howson JMM, O'Donnell CJ, Spector T, Nalls MA, Simonsick EM, Liu Y, van Duijn CM, Butterworth AS, Danesh JN, Menni C, Wareham NJ, Khaw K-T, Sun YV, Wilson PWF, Cho K, Visscher PM, Denny JC, Levy D, Edwards TL, Munroe PB, Snieder H, Warren HR
Publication type: Article
Publication status: Published
Journal: Nature Genetics
Year: 2024
Volume: 56
Issue: 5
Pages: 778-791
Print publication date: 01/05/2024
Online publication date: 30/04/2024
Acceptance date: 11/03/2024
Date deposited: 29/05/2024
ISSN (print): 1061-4036
ISSN (electronic): 1546-1718
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41588-024-01714-w
DOI: 10.1038/s41588-024-01714-w
Data Access Statement: Full GWAS summary statistics of our meta-analyses are publicly available on the GWAS Catalog website data repository (https://www.ebi.ac.uk/gwas) with data accession codes GCST90310294, GCST90310295 and GCST90310296 for SBP, DBP and PP, respectively. The SBayesRC PRS data for SBP, DBP and PP are deposited on the PGS Catalog website (https://www.pgscatalog.org), with data accession codes PGS004603, PGS004604 and PGS004605 for SBP, DBP and PP, respectively, alongside publication ID PGP000581. The standard clumping and threshold PRSs for SBP, DBP and PP; summary statistics for sentinel SNPs for each BP trait as well as optimized PRS; and statistically significant reports for S-PrediXcan results for all five tissues for all BP traits evaluated are available in the Supplementary Tables. Code availability: All software programs used in the study are publicly available as described in Methods and the Reporting Summary.
PubMed id: 38689001
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