Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits
Published: 25 March 2024
New article from Professor Dame Anna Dominiczak
Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits
Jacob M. Keaton, Zoha Kamali, Tian Xie, Ahmad Vaez, Ariel Williams, Slavina B. Goleva, Alireza Ani, Evangelos Evangelou, Jacklyn N. Hellwege, Loic Yengo, William J. Young, Matthew Traylor, Ayush Giri, Zhili Zheng, Jian Zeng, Daniel I. Chasman, Andrew P. Morris, Mark J. Caulfield, Shih-Jen Hwang, Jaspal S. Kooner, David Conen, John R. Attia, Alanna C. Morrison, Ruth J.F. Loos, Kati Kristiansson, Reinhold Schmidt, Andrew A. Hicks, Peter P. Pramstaller, Christopher P. Nelson, Nilesh J. Samani, Lorenz Risch, Ulf Gyllensten, Olle Melander, Harriette Riese, James F. Wilson, Harry Campbell, Stephen S. Rich, Bruce M. Psaty, Yingchang Lu, Jerome I. Rotter, Xiuqing Guo, Kenneth M. Rice, Peter Vollenweider, Johan Sundström, Claudia Langenberg, Martin D. Tobin, Vilmantas Giedraitis, Jian'an Luan, Jaakko Tuomilehto, Zoltan Kutalik, Samuli Ripatti, Veikko Salomaa, Giorgia Girotto, Stella Trompet, J. Wouter Jukema, Pim van der Harst, Paul M. Ridker, Franco Giulianini, Veronique Vitart, Anuj Goel, Hugh Watkins, Sarah E. Harris, Ian J. Deary, Peter J. van der Most, Albertine J. Oldehinkel, Bernard D. Keavney, Caroline Hayward, Archie Campbell, Michael Boehnke, Laura J. Scott, Thibaud Boutin, Chrysovalanto Mamasoula, Marjo-Riitta Järvelin, Annette Peters, Christian Gieger, Edward G. Lakatta, Francesco Cucca, Jennie Hui, Paul Knekt, Stefan Enroth, Martin H. De Borst, Ozren Polašek, Maria Pina Concas, Eulalia Catamo, Massimiliano Cocca, Ruifang Li-Gao, Edith Hofer, Helena Schmidt, Beatrice Spedicati, Melanie Waldenberger, David P. Strachan, Maris Laan, Alexander Teumer, Marcus Dörr, Vilmundur Gudnason, James P. Cook, Daniela Ruggiero, Ivana Kolcic, Eric Boerwinkle, Michela Traglia, Terho Lehtimäki, Olli T. Raitakari, Andrew D. Johnson, Christopher Newton-Cheh, Morris J. Brown, Anna F. Dominiczak, Peter J. Sever, Neil Poulter, John C. Chambers, Roberto Elosua, David Siscovick, Tõnu Esko, Andres Metspalu, Rona J. Strawbridge, Markku Laakso, Anders Hamsten, Jouke-Jan Hottenga, Eco de Geus, Andrew D. Morris, Colin N.A. Palmer, Ilja M. Nolte, Yuri Milaneschi, Jonathan Marten, Alan Wright, Eleftheria Zeggini, Joanna M.M. Howson, Christopher J. O'Donnell, Tim Spector, Mike A. Nalls, Eleanor M. Simonsick, Yongmei Liu, Cornelia M. van Duijn, Adam S. Butterworth, John N. Danesh, Cristina Menni, Nicholas J. Wareham, Kay-Tee Khaw, Yan V. Sun, Peter W.F. Wilson, Kelly Cho, Peter M. Visscher, Joshua C. Denny, Million Veterans Program, Lifelines Cohort Study, CHARGE consortium, ICBP Consortium, Daniel Levy, Todd L. Edwards, Patricia B. Munroe, Harold Snieder, and Helen R. Warren
Summary
Hypertension affects >1 billion people worldwide. We identify 113 novel loci, reporting a total of 2,103 independent genetic signals (p<5x10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (N=1,028,980 European individuals). These associations explain >60% of SNP-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRS) 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 seven-fold higher odds of hypertension risk (OR=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 curve (AUC) from 0.791 (95% CI=0.781-0.801) to 0.826 (95% CI=0.817-0.836, ∆AUC=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.
First published: 25 March 2024