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

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.