학술논문
Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits
Document Type
Original Paper
Author
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.; Levy, Daniel; Edwards, Todd L.; Munroe, Patricia B.; Snieder, Harold; Warren, Helen R.
Source
Nature Genetics. 56(5):778-791
Subject
Language
English
ISSN
1061-4036
1546-1718
1546-1718
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.
Genome-wide association analysis in over one million individuals of European ancestry identifies 2,103 independent genetic signals (including 113 new loci) associated with blood pressure traits.
Genome-wide association analysis in over one million individuals of European ancestry identifies 2,103 independent genetic signals (including 113 new loci) associated with blood pressure traits.