@article{9e91c485a59a4a4e89563702496b839d,
title = "Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits",
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.",
author = "{Million Veteran Program} and {LifeLines Cohort Study} and {CHARGE consortium} and {ICBP Consortium} and Keaton, {Jacob M.} and Zoha Kamali and Tian Xie and Ahmad Vaez and Ariel Williams and Goleva, {Slavina B.} and Alireza Ani and Evangelos Evangelou and Hellwege, {Jacklyn N.} and Loic Yengo and Young, {William J.} and Matthew Traylor and Ayush Giri and Zhili Zheng and Jian Zeng and Chasman, {Daniel I.} and Morris, {Andrew P.} and Caulfield, {Mark J.} and Hwang, {Shih Jen} and Kooner, {Jaspal S.} and David Conen and Attia, {John R.} and Morrison, {Alanna C.} and Loos, {Ruth J.F.} and Kati Kristiansson and Reinhold Schmidt and Hicks, {Andrew A.} and Pramstaller, {Peter P.} and Nelson, {Christopher P.} and Samani, {Nilesh J.} and Lorenz Risch and Ulf Gyllensten and Olle Melander and Harriette Riese and Wilson, {James F.} and Harry Campbell and Rich, {Stephen S.} and Psaty, {Bruce M.} and Yingchang Lu and Rotter, {Jerome I.} and Xiuqing Guo and Rice, {Kenneth M.} and Peter Vollenweider and Johan Sundstr{\"o}m and Claudia Langenberg and Tobin, {Martin D.} and Vilmantas Giedraitis and Jian'an Luan and Jaakko Tuomilehto and Zoltan Kutalik and Samuli Ripatti and Veikko Salomaa and Giorgia Girotto and Stella Trompet and Jukema, {J. Wouter} and {van der Harst}, Pim and Ridker, {Paul M.} and Franco Giulianini and Veronique Vitart and Anuj Goel and Hugh Watkins and Harris, {Sarah E.} and Deary, {Ian J.} and {van der Most}, {Peter J.} and Oldehinkel, {Albertine J.} and Keavney, {Bernard D.} and Caroline Hayward and Archie Campbell and Michael Boehnke and Scott, {Laura J.} and Thibaud Boutin and Chrysovalanto Mamasoula and J{\"a}rvelin, {Marjo Riitta} and Annette Peters and Christian Gieger and Lakatta, {Edward G.} and Francesco Cucca and Jennie Hui and Paul Knekt and Stefan Enroth and {De Borst}, {Martin H.} and Ozren Pola{\v s}ek and Concas, {Maria Pina} and Eulalia Catamo and Massimiliano Cocca and Ruifang Li-Gao and Edith Hofer and Helena Schmidt and Beatrice Spedicati and Melanie Waldenberger and Strachan, {David P.} and Maris Laan and Alexander Teumer and Marcus D{\"o}rr and Vilmundur Gudnason and Cook, {James P.} and Daniela Ruggiero and Ivana Kolcic and Eric Boerwinkle and Michela Traglia and Terho Lehtim{\"a}ki and Raitakari, {Olli T.} and Johnson, {Andrew D.} and Christopher Newton-Cheh and Brown, {Morris J.} and Dominiczak, {Anna F.} and Sever, {Peter J.} and Neil Poulter and Chambers, {John C.} and Roberto Elosua and David Siscovick and T{\~o}nu Esko and Andres Metspalu and Strawbridge, {Rona J.} and Markku Laakso and Anders Hamsten and Hottenga, {Jouke Jan} and {de Geus}, Eco and Morris, {Andrew D.} and Palmer, {Colin N.A.} and Nolte, {Ilja M.} and Yuri Milaneschi and Jonathan Marten and Alan Wright and Eleftheria Zeggini and Howson, {Joanna M.M.} and O'Donnell, {Christopher J.} and Tim Spector and Nalls, {Mike A.} and Simonsick, {Eleanor M.} and Yongmei Liu and {van Duijn}, {Cornelia M.} and Butterworth, {Adam S.} and Danesh, {John N.} and Cristina Menni and Wareham, {Nicholas J.} and Khaw, {Kay Tee} and Sun, {Yan V.} and Wilson, {Peter W.F.} and Kelly Cho and Visscher, {Peter M.} and Denny, {Joshua C.} and Daniel Levy and Edwards, {Todd L.} and Munroe, {Patricia B.} and Harold Snieder and Warren, {Helen R.}",
note = "Publisher Copyright: {\textcopyright} 2024. The Author(s).",
year = "2024",
month = may,
doi = "10.1038/s41588-024-01714-w",
language = "English",
volume = "56",
pages = "778--791",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group - Macmillan Publishers",
number = "5",
}