The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Georg Ehret, Teresa Ferreira, Daniel I. Chasman, Anne U. Jackson, Ellen M. Schmidt, Toby Johnson, Gudmar Thorleifsson, Jian'an Luan, Louise A. Donnelly, Stavroula Kanoni, Ann Kristin Petersen, Vasyl Pihur, Rona J. Strawbridge, Dmitry Shungin, Maria F. Hughes, Osorio Meirelles, Marika Kaakinen, Nabila Bouatia-Naji, Kati Kristiansson, Sonia ShahMarcus E. Kleber, X. Guo, Leo Pekka Lyytikäinen, Cristiano Fava, Niclas Eriksson, Ilja M. Nolte, Patrik K E Magnusson, Elias Salfati, Loukianos S. Rallidis, Elizabeth Theusch, Andrew J P Smith, Lasse Folkersen, Kate Witkowska, Tune H. Pers, Roby Joehanes, Stuart K. Kim, Lazaros Lataniotis, Rick Jansen, Andrew D. Johnson, Helen R. Warren, Young Jin Kim, Wei Zhao, Ying Wu, Bamidele O. Tayo, Murielle Bochud, Devin Absher, Linda S. Adair, Najaf Amin, Dan E. Arking, Tomas Axelsson, Damiano Baldassarre, Beverley Balkau, S. Bandinelli, Michael R. Barnes, Inês Barroso, Stephen Bevan, Joshua Bis, Gyda Bjornsdottir, Michael Boehnke, Eric Boerwinkle, Lori L. Bonnycastle, Dorret I. Boomsma, Stefan R. Bornstein, M. J. Brown, Michel Burnier, Claudia Cabrera, John C. Chambers, I. Shou Chang, Ching Yu Cheng, Peter S. Chines, Ren Hua Chung, Francis S. Collins, John M. Connell, Angela Döring, Jean Dallongeville, John Danesh, Ulf de Faire, Graciela Delgado, Anna Dominiczak, Alex S F Doney, Fotios Drenos, Sarah Edkins, John D. Eicher, Roberto Elosua, Stefan Enroth, Jeanette Erdmann, Per Eriksson, Tõnu Esko, Evangelos Evangelou, Alun Evans, Tove Fall, Martin Farrall, Janine F. Felix, Jean Ferrières, L. Ferrucci, Myriam Fornage, Terrence Forrester, Nora Franceschini, Oscar H. Franco, Anders Franco-Cereceda, Ross M. Fraser, Santhi K. Ganesh, He Gao, Karl Gertow, Francesco Gianfagna, Bruna Gigante, Franco Giulianini, Anuj Goel, Alison H. Goodall, Mark O. Goodarzi, Mathias Gorski, Jürgen Gräßler, Christopher J. Groves, Vilmundur Gudnason, Ulf Gyllensten, Göran Hallmans, Anna Liisa Hartikainen, Maija Hassinen, Aki S. Havulinna, Caroline Hayward, Serge Hercberg, Karl Heinz Herzig, Andrew A. Hicks, A. Hingorani, Joel N. Hirschhorn, Albert Hofman, Jostein Holmen, Oddgeir Holmen, Jouke Jan Hottenga, Philip J. Howard, Chao Agnes Hsiung, Steven C. Hunt, M. Arfan Ikram, Thomas Illig, Carlos Iribarren, Richard A. Jensen, Mika Kähönen, Hyun Min Kang, Sekar Kathiresan, Brendan J. Keating, Kay Thee Khaw, Yun Kyoung Kim, Eric Kim, Mika Kivimaki, Norman Klopp, Genovefa Kolovou, Pirjo Komulainen, Jaspal S. Kooner, Gulum Kosova, Ronald M. Krauss, Diana Kuh, Zoltán Kutalik, Johanna Kuusisto, Kirsti Kvaløy, Timo A. Lakka, Nanette R. Lee, I. T. Lee, Wen Jane Lee, Daniel Levy, Xiaohui Li, Kae Woei Liang, Honghuang Lin, Li Lin, Jaana Lindström, Stéphane Lobbens, Satu Männistö, Gabriele Müller, Martina Müller-Nurasyid, François Mach, H. S. Markus, Eirini Marouli, Mark I. McCarthy, Colin A. McKenzie, Pierre Meneton, Cristina Menni, Andres Metspalu, Vladan Mijatovic, Leena Moilanen, May E. Montasser, Andrew D. Morris, Alanna Morrison, Antonella Mulas, Ramaiah Nagaraja, Narisu Narisu, K. Nikus, Christopher J. O'Donnell, Paul F. O'Reilly, Ken K. Ong, F. Paccaud, Cameron D. Palmer, Afshin Parsa, N. L. Pedersen, Brenda W. Penninx, Markus Perola, Annette Peters, Neil Poulter, Peter P. Pramstaller, Bruce M. Psaty, Thomas Quertermous, D. C. Rao, Asif Rasheed, Nigel W. Rayner, Frida Renstrom, Rainer Rettig, Kenneth Rice, Robert Roberts, Lynda M. Rose, J. Rossouw, Nilesh J. Samani, S. Sanna, Jouko Saramies, Heribert Schunkert, Sylvain Sebert, Wayne H H Sheu, Young Ah Shin, Xueling Sim, Johannes H. Smit, Albert V. Smith, Maria X. Sosa, Tim D. Spector, Alena Stančáková, Alice V. Stanton, Kathleen Stirrups, Heather M. Stringham, Johan Sundström, Amy J. Swift, Ann Christine Syvänen, E. Shyong Tai, Toshiko Tanaka, Kirill V. Tarasov, Alexander Teumer, Unnur Thorsteinsdóttir, Martin D. Tobin, Elena Tremoli, Andre G. Uitterlinden, Matti Uusitupa, Ahmad Vaez, Dhananjay Vaidya, Cornelia M. Van Duijn, Erik P A Van Iperen, Ramachandran S. Vasan, Germaine C. Verwoert, Jarmo Virtamo, Veronique Vitart, Benjamin F. Voight, Peter Vollenweider, Aline Wagner, Louise V. Wain, N. J. Wareham, H. Watkins, Alan B. Weder, Harm Jan Westra, Rainford J. Wilks, Tom Wilsgaard, James F. Wilson, Tien Y. Wong, Tsun Po Yang, Jie Yao, Loic Yengo, Weihua Zhang, Jing Hua Zhao, Xiaofeng Zhu, Pascal Bovet, Richard S. Cooper, Karen L. Mohlke, Danish Saleheen, Jong Young Lee, Paul Elliott, Hinco J. Gierman, Cristen J. Willer, L. Franke, G. Kees Hovingh, Kent D. Taylor, George Dedoussis, Peter Sever, Andrew Wong, Lars Lind, Themistocles L. Assimes, Inger Njølstad, Peter E H Schwarz, Claudia Langenberg, Harold Snieder, Mark J. Caulfield, Olle Melander, Markku Laakso, Juha Saltevo, Rainer Rauramaa, Jaakko Tuomilehto, Erik Ingelsson, Terho Lehtimäki, Kristian Hveem, Walter Palmas, Winfried März, M. Kumari, Veikko Salomaa, Yii Der Ida Chen, J. Rotter, Philippe Froguel, Marjo Riitta Jarvelin, E. G. Lakatta, Kari Kuulasmaa, Paul W. Franks, A. Hamsten, H. Erich Wichmann, Colin N A Palmer, Kari Stefansson, Paul M. Ridker, Ruth J F Loos, Aravinda Chakravarti, Panos Deloukas, Andrew P. Morris, Christopher Newton-Cheh, Patricia B. Munroe

Research output: Contribution to journalArticle

Abstract

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

Original languageEnglish
Pages (from-to)1171-1184
Number of pages14
JournalNature Genetics
Volume48
Issue number10
DOIs
Publication statusPublished - Oct 1 2016

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals'. Together they form a unique fingerprint.

  • Cite this

    Ehret, G., Ferreira, T., Chasman, D. I., Jackson, A. U., Schmidt, E. M., Johnson, T., Thorleifsson, G., Luan, J., Donnelly, L. A., Kanoni, S., Petersen, A. K., Pihur, V., Strawbridge, R. J., Shungin, D., Hughes, M. F., Meirelles, O., Kaakinen, M., Bouatia-Naji, N., Kristiansson, K., ... Munroe, P. B. (2016). The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nature Genetics, 48(10), 1171-1184. https://doi.org/10.1038/ng.3667