Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits-Reference-Cited by-同舟云学术

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

Published:2024-04-30 Issue:5 Volume:56 Page:778-791
ISSN:1061-4036
Container-title:Nature Genetics
language:en
Short-container-title:Nat Genet

Author:

Keaton Jacob M.,Kamali Zoha^ORCID,Xie Tian^ORCID,Vaez Ahmad^ORCID,Williams Ariel,Goleva Slavina B.^ORCID,Ani Alireza^ORCID,Evangelou Evangelos^ORCID,Hellwege Jacklyn N.^ORCID,Yengo Loic,Young William J.^ORCID,Traylor Matthew,Giri Ayush,Zheng Zhili^ORCID,Zeng Jian,Chasman Daniel I.,Morris Andrew P.^ORCID,Caulfield Mark J.^ORCID,Hwang Shih-Jen,Kooner Jaspal S.^ORCID,Conen David,Attia John R.^ORCID,Morrison Alanna C.^ORCID,Loos Ruth J. F.^ORCID,Kristiansson Kati,Schmidt Reinhold,Hicks Andrew A.^ORCID,Pramstaller Peter P.^ORCID,Nelson Christopher P.,Samani Nilesh J.,Risch Lorenz^ORCID,Gyllensten Ulf^ORCID,Melander Olle,Riese Harriette,Wilson James F.^ORCID,Campbell Harry,Rich Stephen S.^ORCID,Psaty Bruce M.^ORCID,Lu Yingchang,Rotter Jerome I.^ORCID,Guo Xiuqing^ORCID,Rice Kenneth M.^ORCID,Vollenweider Peter,Sundström Johan,Langenberg Claudia^ORCID,Tobin Martin D.^ORCID,Giedraitis Vilmantas^ORCID,Luan Jian’an^ORCID,Tuomilehto Jaakko,Kutalik Zoltan,Ripatti Samuli^ORCID,Salomaa Veikko^ORCID,Girotto Giorgia^ORCID,Trompet Stella^ORCID,Jukema J. Wouter,van der Harst Pim,Ridker Paul M.,Giulianini Franco,Vitart Veronique^ORCID,Goel Anuj^ORCID,Watkins Hugh^ORCID,Harris Sarah E.^ORCID,Deary Ian J.^ORCID,van der Most Peter J.^ORCID,Oldehinkel Albertine J.^ORCID,Keavney Bernard D.^ORCID,Hayward Caroline^ORCID,Campbell Archie^ORCID,Boehnke Michael^ORCID,Scott Laura J.^ORCID,Boutin Thibaud^ORCID,Mamasoula Chrysovalanto,Järvelin Marjo-Riitta,Peters Annette^ORCID,Gieger Christian^ORCID,Lakatta Edward G.^ORCID,Cucca Francesco^ORCID,Hui Jennie,Knekt Paul,Enroth Stefan^ORCID,De Borst Martin H.^ORCID,Polašek Ozren,Concas Maria Pina,Catamo Eulalia^ORCID,Cocca Massimiliano^ORCID,Li-Gao Ruifang,Hofer Edith,Schmidt Helena^ORCID,Spedicati Beatrice^ORCID,Waldenberger Melanie^ORCID,Strachan David P.,Laan Maris^ORCID,Teumer Alexander^ORCID,Dörr Marcus,Gudnason Vilmundur^ORCID,Cook James P.,Ruggiero Daniela^ORCID,Kolcic Ivana^ORCID,Boerwinkle Eric,Traglia Michela,Lehtimäki Terho,Raitakari Olli T.,Johnson Andrew D.^ORCID,Newton-Cheh Christopher^ORCID,Brown Morris J.^ORCID,Dominiczak Anna F.^ORCID,Sever Peter J.,Poulter Neil,Chambers John C.^ORCID,Elosua Roberto,Siscovick David,Esko Tõnu,Metspalu Andres^ORCID,Strawbridge Rona J.^ORCID,Laakso Markku^ORCID,Hamsten Anders,Hottenga Jouke-Jan^ORCID,de Geus Eco,Morris Andrew D.,Palmer Colin N. A.^ORCID,Nolte Ilja M.^ORCID,Milaneschi Yuri^ORCID,Marten Jonathan,Wright Alan,Zeggini Eleftheria^ORCID,Howson Joanna M. M.^ORCID,O’Donnell Christopher J.,Spector Tim^ORCID,Nalls Mike A.^ORCID,Simonsick Eleanor M.,Liu Yongmei,van Duijn Cornelia M.^ORCID,Butterworth Adam S.^ORCID,Danesh John N.,Menni Cristina^ORCID,Wareham Nicholas J.^ORCID,Khaw Kay-Tee,Sun Yan V.^ORCID,Wilson Peter W. F.^ORCID,Cho Kelly,Visscher Peter M.^ORCID,Denny Joshua C.^ORCID, , , ,van Duijn Cornelia M., ,Butterworth Adam S.,Vaez Ahmad,Teumer Alexander,Johnson Andrew D.,Morris Andrew D.,Peters Annette,Goel Anuj,Campbell Archie,Keavney Bernard D.,Hayward Caroline,Newton-Cheh Christopher,Nelson Christopher P.,Chasman Daniel I.,Levy Daniel,Ruggiero Daniela,de Geus Eco,Hofer Edith,Zeggini Eleftheria,Boerwinkle Eric,Girotto Giorgia,Warren Helen R.,Watkins Hugh,Kolcic Ivana,Jukema J. Wouter,Hui Jennie,Howson Joanna M. M.,Sundström Johan,Chambers John C.,Danesh John N.,Risch Lorenz,Caulfield Mark J.,Laakso Markku,Tobin Martin D.,De Borst Martin H.,Waldenberger Melanie,Samani Nilesh J.,Melander Olle,Raitakari Olli T.,Polašek Ozren,Munroe Patricia B.,Ridker Paul M.,van der Harst Pim,Elosua Roberto,Ripatti Samuli,Lehtimäki Terho,Young William J.,Kamali Zoha,Kutalik Zoltan,Levy Daniel,Edwards Todd L.^ORCID,Munroe Patricia B.^ORCID,Snieder Harold^ORCID,Warren Helen R.^ORCID

Abstract

AbstractHypertension 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.

Publisher

Springer Science and Business Media LLC

Link

https://www.nature.com/articles/s41588-024-01714-w.pdf

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