Genome-wide analysis in over 1 million individuals reveals over 2,000 independent genetic signals for blood pressure

Helen R. Warren; Todd L. Edwards; Ahmad Vaez; Jacob M. Keaton; Zoha Kamali; Tian Xie; Alireza Ani; Εvangelos Εvangelou; Jacklyn N. Hellwege; Loïc Yengo; William J. Young; Matthew Traylor; Ayush Giri; Peter M. Visscher; Daniel I. Chasman; Andrew P. Morris; Mark J. Caulfield; Shih‐Jen Hwang; Jaspal S. Kooner; David Conen; John 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; Harriëtte Riese; James F. Wilson; Harry Campbell; Bruce M. Psaty; Yingchang Lu; Jerome I. Rotter; Xiuqing Guo; Kenneth Rice; Péter Vollenweider; Johan Sundström; Claudia Langenberg; Martin D. Tobin; Vilmantas Giedraitis; Jian’an Luan; Jaakko Tuomilehto; Zoltán Kutalik; Samuli Ripatti; Veikko Salomaa; Giorgia Girotto; Stella Trompet; J. Wouter Jukema; Pim van der Harst; Paul M. Ridker; Franco Giulianini; Véronique Vitart; Anuj Goel; Hugh Watkins; Sarah E. Harris; Ian J. Deary; Peter J. van der Most; Albertine J. Oldehinkel; Bernard Keavney; Caroline Hayward; A.M. Campbell; Michael Boehnke; Laura J. Scott; Thibaud Boutin; Chrysovalanto Mamasoula; Paul M Ridker; 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; Mélanie Waldenberger; David P. Strachan; Maris Laan; Alexander Teumer; Marcus Dörr; Vilmundur Guðnason; James P. Cook; Daniela Ruggiero; Ivana Kolčić; Eric Boerwinkle; Michela Traglia; Terho Lehtimäki; Olli T. Raitakari

doi:10.21203/rs.3.rs-1409164/v1

Paul M Ridker

Harvard University

Abstract

Abstract Hypertension is a leading cause of premature death affecting more than a billion individuals worldwide. Here we report on the genetic determinants of blood pressure (BP) traits (systolic, diastolic, and pulse pressure) in the largest single-stage genome-wide analysis to date (N = 1,028,980 European-descent individuals). We identified 2,103 independent genetic signals (P < 5x10^{− 8}) for BP traits, including 113 novel loci. These associations explain ~ 40% of common SNP heritability of systolic and diastolic BP. Comparison of top versus bottom deciles of polygenic risk scores (PRS) based on these results reveal clinically meaningful differences in BP (12.9 mm Hg for systolic BP, 95% CI 11.5–14.2 mm Hg, p = 9.08×10^{− 73}) and hypertension risk (OR 5.41; 95% CI 4.12 to 7.10; P = 9.71×10^{− 33}) in an independent dataset. Compared with the area under the curve (AUC) for hypertension discrimination for a model with sex, age, BMI, and genetic ancestry, adding systolic and diastolic BP PRS increased discrimination from 0.791 (95% CI = 0.781–0.801) to 0.814 (95% CI = 0.805–0.824, ∆AUC = 0.023, P = 2.27x10^{− 22}). Our transcriptome-wide association study detected 2,793 BP colocalized associations with genetically-predicted expression of 1,070 genes in five cardiovascular tissues, of which 500 are previously unreported for BP traits. These findings represent an advance in our understanding of hypertension and highlight the role of increasingly large genomic studies for development of more accurate PRS, which may inform precision health research.

How to cite this publication

Helen R. Warren, Todd L. Edwards, Ahmad Vaez, Jacob M. Keaton, Zoha Kamali, Tian Xie, Alireza Ani, Εvangelos Εvangelou, Jacklyn N. Hellwege, Loïc Yengo, William J. Young, Matthew Traylor, Ayush Giri, Peter M. Visscher, Daniel I. Chasman, Andrew P. Morris, Mark J. Caulfield, Shih‐Jen Hwang, Jaspal S. Kooner, David Conen, John 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, Harriëtte Riese, James F. Wilson, Harry Campbell, Bruce M. Psaty, Yingchang Lu, Jerome I. Rotter, Xiuqing Guo, Kenneth Rice, Péter Vollenweider, Johan Sundström, Claudia Langenberg, Martin D. Tobin, Vilmantas Giedraitis, Jian’an Luan, Jaakko Tuomilehto, Zoltán Kutalik, Samuli Ripatti, Veikko Salomaa, Giorgia Girotto, Stella Trompet, J. Wouter Jukema, Pim van der Harst, Paul M. Ridker, Franco Giulianini, Véronique Vitart, Anuj Goel, Hugh Watkins, Sarah E. Harris, Ian J. Deary, Peter J. van der Most, Albertine J. Oldehinkel, Bernard Keavney, Caroline Hayward, A.M. Campbell, Michael Boehnke, Laura J. Scott, Thibaud Boutin, Chrysovalanto Mamasoula, Paul M Ridker, 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, Mélanie Waldenberger, David P. Strachan, Maris Laan, Alexander Teumer, Marcus Dörr, Vilmundur Guðnason, James P. Cook, Daniela Ruggiero, Ivana Kolčić, Eric Boerwinkle, Michela Traglia, Terho Lehtimäki, Olli T. Raitakari (2022). Genome-wide analysis in over 1 million individuals reveals over 2,000 independent genetic signals for blood pressure. , DOI: https://doi.org/10.21203/rs.3.rs-1409164/v1.

Genome-wide analysis in over 1 million individuals reveals over 2,000 independent genetic signals for blood pressure

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Paul M Ridker

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