Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Georg B. Ehret, Patricia B. Munroe, Kenneth M. Rice, Murielle Bochud, Andrew D. Johnson, Daniel I. Chasman, Albert V. Smith, Martin D. Tobin, Germaine C. Verwoert, Shih Jen Hwang, Vasyl Pihur, Peter Vollenweider, Paul F. O'Reilly, Najaf Amin, Jennifer L. Bragg-Gresham, Alexander Teumer, Nicole L. Glazer, Lenore Launer, Jing Hua Zhao, Yurii AulchenkoSimon Heath, Siim Sober, Afshin Parsa, Jian'an Luan, Pankaj Arora, Abbas Dehghan, Feng Zhang, Gavin Lucas, Andrew A. Hicks, Anne U. Jackson, John F. Peden, Toshiko Tanaka, Sarah H. Wild, Igor Rudan, Wilmar Igl, Yuri Milaneschi, Alex N. Parker, Cristiano Fava, John C. Chambers, Ervin R. Fox, Meena Kumari, Min Jin Go, Pim van der Harst, Wen Hong Linda Kao, Marketa Sjögren, D. G. Vinay, Myriam Alexander, Yasuharu Tabara, Sue Shaw-Hawkins, Peter H. Whincup, Yongmei Liu, Gang Shi, Johanna Kuusisto, Bamidele Tayo, Mark Seielstad, Xueling Sim, Khanh Dung Hoang Nguyen, Terho Lehtimäki, Giuseppe Matullo, Ying Wu, Tom R. Gaunt, N. Charlotte Onland-Moret, Matthew N. Cooper, Carl G.P. Platou, Elin Org, Rebecca Hardy, Santosh Dahgam, Jutta Palmen, Veronique Vitart, Peter S. Braund, Tatiana Kuznetsova, Cuno S.P.M. Uiterwaal, Adebowale Adeyemo, Walter Palmas, Harry Campbell, Barbara Ludwig, Maciej Tomaszewski, Ioanna Tzoulaki, Nicholette D. Palmer, Thor Aspelund, Melissa Garcia, Yen Pei C. Chang, Jeffrey R. O'Connell, Nanette I. Steinle, Diederick E. Grobbee, Dan E. Arking, Sharon L. Kardia, Alanna C. Morrison, Dena Hernandez, Samer Najjar, Wendy L. McArdle, David Hadley, Morris J. Brown, John M. Connell, Aroon D. Hingorani, Ian N.M. Day, Debbie A. Lawlor, John P. Beilby, Robert W. Lawrence, Robert Clarke, Jemma C. Hopewell, Halit Ongen, Albert W. Dreisbach, Yali Li, J. Hunter Young, Joshua C. Bis, Mika Kähönen, Jorma Viikari, Linda S. Adair, Nanette R. Lee, Ming Huei Chen, Matthias Olden, Cristian Pattaro, Judith A.Hoffman Bolton, Anna Köttgen, Sven Bergmann, Vincent Mooser, Nish Chaturvedi, Timothy M. Frayling, Muhammad Islam, Tazeen H. Jafar, Jeanette Erdmann, Smita R. Kulkarni, Stefan R. Bornstein, Jürgen Grässler, Leif Groop, Benjamin F. Voight, Johannes Kettunen, Philip Howard, Andrew Taylor, Simonetta Guarrera, Fulvio Ricceri, Valur Emilsson, Andrew Plump, Inês Barroso, Kay Tee Khaw, Alan B. Weder, Steven C. Hunt, Yan V. Sun, Richard N. Bergman, Francis S. Collins, Lori L. Bonnycastle, Laura J. Scott, Heather M. Stringham, Leena Peltonen, Markus Perola, Erkki Vartiainen, Stefan Martin Brand, Jan A. Staessen, Thomas J. Wang, Paul R. Burton, Maria Soler Artigas, Yanbin Dong, Harold Snieder, Xiaoling Wang, Haidong Zhu, Kurt K. Lohman, Megan E. Rudock, Susan R. Heckbert, Nicholas L. Smith, Kerri L. Wiggins, Ayo Doumatey, Daniel Shriner, Gudrun Veldre, Margus Viigimaa, Sanjay Kinra, Dorairaj Prabhakaran, Vikal Tripathy, Carl D. Langefeld, Annika Rosengren, Dag S. Thelle, Anna Maria Corsi, Andrew Singleton, Terrence Forrester, Gina Hilton, Colin A. McKenzie, Tunde Salako, Naoharu Iwai, Yoshikuni Kita, Toshio Ogihara, Takayoshi Ohkubo, Tomonori Okamura, Hirotsugu Ueshima, Satoshi Umemura, Susana Eyheramendy, Thomas Meitinger, H. Erich Wichmann, Yoon Shin Cho, Hyung Lae Kim, Jong Young Lee, James Scott, Joban S. Sehmi, Weihua Zhang, Bo Hedblad, Peter Nilsson, George Davey Smith, Andrew Wong, Narisu Narisu, Alena Stančáková, Leslie J. Raffel, Jie Yao, Sekar Kathiresan, Christopher J. O'Donnell, Stephen M. Schwartz, M. Arfan Ikram, W. T. Longstreth, Thomas H. Mosley, Sudha Seshadri, Nick R.G. Shrine, Louise V. Wain, Mario A. Morken, Amy J. Swift, Jaana Laitinen, Inga Prokopenko, Paavo Zitting, Jackie A. Cooper, Steve E. Humphries, John Danesh, Asif Rasheed, Anuj Goel, Anders Hamsten, Hugh Watkins, Stephan J.L. Bakker, Wiek H. van Gilst, Charles S. Janipalli, K. Radha Mani, Chittaranjan S. Yajnik, Albert Hofman, Francesco U.S. Mattace-Raso, Ben A. Oostra, Ayse Demirkan, Aaron Isaacs, Fernando Rivadeneira, Edward G. Lakatta, Marco Orru, Angelo Scuteri, Mika Ala-Korpela, Antti J. Kangas, Leo Pekka Lyytikäinen, Pasi Soininen, Taru Tukiainen, Peter Würtz, Rick Twee-HeeOng, Marcus Dörr, Heyo K. Kroemer, Uwe Völker, Henry Völzke, Pilar Galan, Serge Hercberg, Mark Lathrop, Diana Zelenika, Panos Deloukas, Massimo Mangino, Tim D. Spector, Guangju Zhai, James F. Meschia, Michael A. Nalls, Pankaj Sharma, Janos Terzic, M. V. Kranthi Kumar, Matthew Denniff, Ewa Zukowska-Szczechowska, Lynne E. Wagenknecht, F. Gerald R. Fowkes, Fadi J. Charchar, Peter E.H. Schwarz, Caroline Hayward, Xiuqing Guo, Charles Rotimi, Michiel L. Bots, Eva Brand, Nilesh J. Samani, Ozren Polasek, Philippa J. Talmud, Fredrik Nyberg, Diana Kuh, Maris Laan, Kristian Hveem, Lyle J. Palmer, Yvonne T. van der Schouw, Juan P. Casas, Karen L. Mohlke, Paolo Vineis, Olli Raitakari, Santhi K. Ganesh, Tien Y. Wong, E. Shyong Tai, Richard S. Cooper, Markku Laakso, Dabeeru C. Rao, Tamara B. Harris, Richard W. Morris, Anna F. Dominiczak, Mika Kivimaki, Michael G. Marmot, Tetsuro Miki, Danish Saleheen, Giriraj R. Chandak, Josef Coresh, Gerjan Navis, Veikko Salomaa, Bok Ghee Han, Xiaofeng Zhu, Jaspal S. Kooner, Olle Melander, Paul M. Ridker, Stefania Bandinelli, Ulf B. Gyllensten, Alan F. Wright, James F. Wilson, Luigi Ferrucci, Martin Farrall, Jaakko Tuomilehto, Peter P. Pramstaller, Roberto Elosua, Nicole Soranzo, Eric J.G. Sijbrands, David Altshuler, Ruth J.F. Loos, Alan R. Shuldiner, Christian Gieger, Pierre Meneton, Andre G. Uitterlinden, Nicholas J. Wareham, Vilmundur Gudnason, Jerome I. Rotter, Rainer Rettig, Manuela Uda, David P. Strachan, Jacqueline C.M. Witteman, Anna Liisa Hartikainen, Jacques S. Beckmann, Eric Boerwinkle, Ramachandran S. Vasan, Michael Boehnke, Martin G. Larson, Marjo Riitta Järvelin, Bruce M. Psaty, Gonçalo R. Abecasis, Aravinda Chakravarti, Paul Elliott, Cornelia M. van Duijn, Christopher Newton-Cheh, Daniel Levy, Mark J. Caulfield, Toby Johnson

Research output: Contribution to journalArticle

1333 Scopus citations

Abstract

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140mmg Hg systolic blood pressure ≥90mmg Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3 GUCY1B3, NPR3 C5orf23, ADM, FURIN FES, GOSR2, GNAS EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

Original languageEnglish (US)
Pages (from-to)103-109
Number of pages7
JournalNature
Volume478
Issue number7367
DOIs
StatePublished - Oct 6 2011

ASJC Scopus subject areas

  • General

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    Ehret, G. B., Munroe, P. B., Rice, K. M., Bochud, M., Johnson, A. D., Chasman, D. I., Smith, A. V., Tobin, M. D., Verwoert, G. C., Hwang, S. J., Pihur, V., Vollenweider, P., O'Reilly, P. F., Amin, N., Bragg-Gresham, J. L., Teumer, A., Glazer, N. L., Launer, L., Zhao, J. H., ... Johnson, T. (2011). Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature, 478(7367), 103-109. https://doi.org/10.1038/nature10405