Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

Helen R. Warren, Evangelos Evangelou, Claudia P. Cabrera, He Gao, Meixia Ren, Borbala Mifsud, Ioanna Ntalla, Praveen Surendran, Chunyu Liu, James P. Cook, Aldi T. Kraja, Fotios Drenos, Marie Loh, Niek Verweij, Jonathan Marten, Ibrahim Karaman, Marcelo P. Segura Lepe, Paul O'Reilly, Joanne Knight, Harold Snieder & 249 others Norihiro Kato, Jiang He, E. Shyong Tai, M. Abdullah Said, David Porteous, Maris Alver, Neil Poulter, Martin Farrall, Ron T. Gansevoort, Sandosh Padmanabhan, Reedik Mägi, Alice Stanton, John Connell, Stephan J.L. Bakker, Andres Metspalu, Denis C. Shields, Simon Thom, Morris Brown, Peter Sever, Tõnu Esko, Caroline Hayward, Pim van der Harst, Danish Saleheen, Rajiv Chowdhury, John C. Chambers, Daniel I. Chasman, Aravinda Chakravarti, Christopher Newton-Cheh, Cecilia M. Lindgren, Daniel Levy, Jaspal S. Kooner, Bernard D. Keavney, Maciej Tomaszewski, Nilesh J. Samani, Joanna M.M. Howson, Martin D. Tobin, Patricia B. Munroe, Georg B. Ehret, V. Wain, Michael R. Barnes, Ioanna Tzoulaki, Mark J. Caulfield, Paul Elliott, V. Wain, Ahmad Vaez, Rick Jansen, Roby Joehanes, Peter J. van der Most, A. Mesut Erzurumluoglu, Paul O'Reilly, Lynda M. Rose, Germaine C. Verwoert, Jouke Jan Hottenga, Rona J. Strawbridge, Tonu Esko, Dan E. Arking, Shih Jen Hwang, Xiuqing Guo, Zoltan Kutalik, Stella Trompet, Nick Shrine, Alexander Teumer, Janina S. Ried, Joshua C. Bis, Albert V. Smith, Najaf Amin, Ilja M. Nolte, Leo Pekka Lyytikäinen, Anubha Mahajan, Nicholas J. Wareham, Edith Hofer, Peter K. Joshi, Kati Kristiansson, Michela Traglia, Aki S. Havulinna, Anuj Goel, Mike A. Nalls, Siim Sõber, Dragana Vuckovic, Jian'an Luan, M. Fabiola Del Greco, Kristin L. Ayers, Jaume Marrugat, Daniela Ruggiero, Lorna M. Lopez, Teemu Niiranen, Stefan Enroth, Anne U. Jackson, Christopher P. Nelson, Jennifer E. Huffman, Weihua Zhang, Ilaria Gandin, Sarah E. Harris, Tatijana Zemonik, Yingchang Lu, Nabi Shah, Martin H. de Borst, Massimo Mangino, Bram P. Prins, Archie Campbell, Ruifang Li-Gao, Ganesh Chauhan, Christopher Oldmeadow, Gonçalo Abecasis, Maryam Abedi, Caterina M. Barbieri, Chiara Batini, Tineka Blake, Michael Boehnke, Erwin P. Bottinger, Peter S. Braund, Marco Brumat, Harry Campbell, Massimiliano Cocca, Francis Collins, Heather J. Cordell, Jeffrey J. Damman, Gail Davies, Eco J. de Geus, Renée de Mutsert, Joris Deelen, Yusuf Demirkale, Alex S.F. Doney, Marcus Dörr, Teresa Ferreira, Mattias Frånberg, Vilmantas Giedraitis, Christian Gieger, Franco Giulianini, Alan J. Gow, Anders Hamsten, Tamara B. Harris, Albert Hofman, Elizabeth G. Holliday, Marjo Riitta Jarvelin, Åsa Johansson, Andrew D. Johnson, Pekka Jousilahti, Antti Jula, Mika Kähönen, Sekar Kathiresan, Kay Tee Khaw, Ivana Kolcic, Seppo Koskinen, Claudia Langenberg, Marty Larson, Lenore J. Launer, Benjamin Lehne, David C.M. Liewald, Li Lin, Lars Lind, François Mach, Chrysovalanto Mamasoula, Cristina Menni, Yuri Milaneschi, Anna Morgan, Andrew D. Morris, Alanna C. Morrison, Peter J. Munson, Priyanka Nandakumar, Quang Tri Nguyen, Teresa Nutile, Albertine J. Oldehinkel, Ben A. Oostra, Elin Org, Aarno Palotie, Guillaume Paré, Alison Pattie, Brenda W.J.H. Penninx, Peter P. Pramstaller, Olli T. Raitakari, Kenneth Rice, Paul M. Ridker, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Jerome I. Rotter, Igor Rudan, Yasaman Saba, Aude Saint Pierre, Cinzia F. Sala, Antti Pekka Sarin, Reinhold Schmidt, Rodney Scott, Marc A. Seelen, David Siscovick, Rossella Sorice, David J. Stott, Johan Sundström, Morris Swertz, Kent D. Taylor, Christophe Tzourio, André G. Uitterlinden, Uwe Völker, Peter Vollenweider, Sarah Wild, Gonneke Willemsen, Alan F. Wright, Jie Yao, Sébastien Thériault, David Conen, Attia John, Stéphanie Debette, Dennis O. Mook-Kanamori, Eleftheria Zeggini, Tim D. Spector, Colin N.A. Palmer, Anne Claire Vergnaud, Ruth J.F. Loos, Ozren Polasek, John M. Starr, Giorgia Girotto, Cecila M. Lindgren, Veronique Vitart, Jaakko Tuomilehto, Ulf Gyllensten, Paul Knekt, Ian J. Deary, Marina Ciullo, Roberto Elosua, Bernard D. Keavney, Andrew A. Hicks, Robert A. Scott, Paolo Gasparini, Maris Laan, Yong Mei Liu, Hugh Watkins, Catharina A. Hartman, Veikko Salomaa, Daniela Toniolo, Markus Perola, James F. Wilson, Helena Schmidt, Jing Hua Zhao, Terho Lehtimäki, Cornelia M. van Duijn, Vilmundur Gudnason, Bruce M. Psaty, Annette Peters, Rainer Rettig, Alan James, J. Wouter Jukema, David P. Strachan, Walter Palmas, Erik Ingelsson, Dorret I. Boomsma, Oscar H. Franco, Murielle Bochud, Andrew P. Morris

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    Abstract

    Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.

    Original languageEnglish
    Pages (from-to)403-415
    Number of pages13
    JournalNature Genetics
    Volume49
    Issue number3
    DOIs
    Publication statusPublished - 1 Mar 2017

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    Warren, H. R., Evangelou, E., Cabrera, C. P., Gao, H., Ren, M., Mifsud, B., ... Morris, A. P. (2017). Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. Nature Genetics, 49(3), 403-415. https://doi.org/10.1038/ng.3768