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Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk
Authors :
Ehret, Georg B. Munroe, Patricia B. Rice, Kenneth M. Bochud, Murielle Johnson, Andrew D. Chasman, Daniel I. Smith, Albert V. Tobin, Martin D. Verwoert, Germaine C. Hwang, Shih-Jen Pihur, Vasyl Vollenweider, Peter O'Reilly, Paul F. Amin, Najaf Bragg-Gresham, Jennifer L. Teumer, Alexander Glazer, Nicole L. Launer, Lenore Zhao, Jing Hua Aulchenko, Yurii Heath, Simon Sober, Siim Parsa, Afshin Luan, Jian'an Arora, Pankaj Dehghan, Abbas Zhang, Feng Lucas, Gavin Hicks, Andrew A. Jackson, Anne U. Peden, John F. Tanaka, Toshiko Wild, Sarah H. Rudan, Igor Igl, Wilmar Milaneschi, Yuri Parker, Alex N. Fava, Cristiano Chambers, John C. Fox, Ervin R. Kumari, Meena Go, Min Jin van der Harst, Pim Kao, Wen Hong Linda Sjogren, Marketa Vinay, D. G. Alexander, Myriam Tabara, Yasuharu Shaw-Hawkins, Sue Whincup, Peter H. Liu, Yongmei Shi, Gang Kuusisto, Johanna Tayo, Bamidele Seielstad, Mark Sim, Xueling Nguyen, Khanh-Dung Hoang Lehtimaki, Terho Matullo, Giuseppe Wu, Ying Gaunt, Tom R. Onland-Moret, N. Charlotte Cooper, Matthew N. Platou, Carl G. P. Org, Elin Hardy, Rebecca Dahgam, Santosh Palmen, Jutta Vitart, Veronique Braund, Peter S. Kuznetsova, Tatiana Uiterwaal, Cuno S. P. M. Adeyemo, Adebowale Palmas, Walter Campbell, Harry Ludwig, Barbara Tomaszewski, Maciej Tzoulaki, Ioanna Palmer, Nicholette D. Aspelund, Thor Garcia, Melissa Chang, Yen-Pei C. O'Connell, Jeffrey R. Steinle, Nanette I. Grobbee, Diederick E. Arking, Dan E. Kardia, Sharon L. Morrison, Alanna C. Hernandez, Dena Najjar, Samer McArdle, Wendy L. Hadley, David Brown, Morris J. Connell, John M. Hingorani, Aroon D. Day, Ian N. M. Lawlor, Debbie A. Beilby, John P. Lawrence, Robert W. Clarke, Robert Hopewell, Jemma C. Ongen, Halit Dreisbach, Albert W. Li, Yali Young, J. Hunter Bis, Joshua C. Kahonen, Mika Viikari, Jorma Adair, Linda S. Lee, Nanette R. Chen, Ming-Huei Olden, Matthias Pattaro, Cristian Bolton, Judith A. Hoffman Koettgen, Anna Bergmann, Sven Mooser, Vincent Chaturvedi, Nish Frayling, Timothy M. Islam, Muhammad Jafar, Tazeen H. Erdmann, Jeanette Kulkarni, Smita R. Bornstein, Stefan R. Graessler, Juergen Groop, Leif Voight, Benjamin F. Kettunen, Johannes Howard, Philip Taylor, Andrew Guarrera, Simonetta Ricceri, Fulvio Emilsson, Valur Plump, Andrew Barroso, Ine S. Khaw, Kay-Tee Weder, Alan B. Hunt, Steven C. Sun, Yan V. Bergman, Richard N. Collins, Francis S. Bonnycastle, Lori L. Scott, Laura J. Stringham, Heather M. Peltonen, Leena Perola, Markus Vartiainen, Erkki Brand, Stefan-Martin Staessen, Jan A. Wang, Thomas J. Burton, Paul R. Artigas, Maria Soler Dong, Yanbin Snieder, Harold Wang, Xiaoling Zhu, Haidong Lohman, Kurt K. Rudock, Megan E. Heckbert, Susan R. Smith, Nicholas L. Wiggins, Kerri L. Doumatey, Ayo Shriner, Daniel Veldre, Gudrun Viigimaa, Margus Kinra, Sanjay Prabhakaran, Dorairaj Tripathy, Vikal Langefeld, Carl D. Rosengren, Annika Thelle, Dag S. Corsi, Anna Maria Singleton, Andrew Forrester, Terrence Hilton, Gina McKenzie, Colin A. Salako, Tunde Iwai, Naoharu Kita, Yoshikuni Ogihara, Toshio Ohkubo, Takayoshi Okamura, Tomonori Ueshima, Hirotsugu Umemura, Satoshi Eyheramendy, Susana Meitinger, Thomas Wichmann, H. -Erich Cho, Yoon Shin Kim, Hyung-Lae Lee, Jong-Young Scott, James Sehmi, Joban S. Zhang, Weihua Hedblad, Bo Nilsson, Peter Smith, George Davey Wong, Andrew Narisu, Narisu Stancakova, Alena Raffel, Leslie J. Yao, Jie Kathiresan, Sekar O'Donnell, Christopher J. Schwartz, Stephen M. Ikram, M. Arfan Longstreth, W. T., Jr. Mosley, Thomas H. Seshadri, Sudha Shrine, Nick R. G. Wain, Louise V. Morken, Mario A. Swift, Amy J. Laitinen, Jaana Prokopenko, Inga Zitting, Paavo Cooper, Jackie A. Humphries, Steve E. Danesh, John Rasheed, Asif Goel, Anuj Hamsten, Anders Watkins, Hugh Bakker, Stephan J. L. van Gilst, Wiek H. Janipalli, Charles S. Mani, K. Radha Yajnik, Chittaranjan S. Hofman, Albert Mattace-Raso, Francesco U. S. Oostra, Ben A. Demirkan, Ayse Isaacs, Aaron Rivadeneira, Fernando Lakatta, Edward G. Orru, Marco Scuteri, Angelo Ala-Korpela, Mika Kangas, Antti J. Lyytikainen, Leo-Pekka Soininen, Pasi Tukiainen, Taru Wurtz, Peter Ong, Rick Twee-Hee Doerr, Marcus Kroemer, Heyo K. Voelker, Uwe Voelzke, Henry Galan, Pilar Hercberg, Serge Lathrop, Mark Zelenika, Diana Deloukas, Panos Mangino, Massimo Spector, Tim D. Zhai, Guangju Meschia, James F. Nalls, Michael A. Sharma, Pankaj Terzic, Janos Kumar, M. V. Kranthi Denniff, Matthew Zukowska-Szczechowska, Ewa Wagenknecht, Lynne E. Fowkes, F. Gerald R. Charchar, Fadi J. Schwarz, Peter E. H. Hayward, Caroline Guo, Xiuqing Rotimi, Charles Bots, Michiel L. Brand, Eva Samani, Nilesh J. Polasek, Ozren Talmud, Philippa J. Nyberg, Fredrik Kuh, Diana Laan, Maris Hveem, Kristian Palmer, Lyle J. van der Schouw, Yvonne T. Casas, Juan P. Mohlke, Karen L. Vineis, Paolo Raitakari, Olli Ganesh, Santhi K. Wong, Tien Y. Tai, E. Shyong Cooper, Richard S. Laakso, Markku Rao, Dabeeru C. Harris, Tamara B. Morris, Richard W. Dominiczak, Anna F. Kivimaki, Mika Marmot, Michael G. Miki, Tetsuro Saleheen, Danish Chandak, Giriraj R. Coresh, Josef Navis, Gerjan Salomaa, Veikko Han, Bok-Ghee Zhu, Xiaofeng Kooner, Jaspal S. Melander, Olle Ridker, Paul M. Bandinelli, Stefania Gyllensten, Ulf B. Wright, Alan F. Wilson, James F. Ferrucci, Luigi Farrall, Martin Tuomilehto, Jaakko Pramstaller, Peter P. Elosua, Roberto Soranzo, Nicole Sijbrands, Eric J. G. Altshuler, David Loos, Ruth J. F. Shuldiner, Alan R. Gieger, Christian Meneton, Pierre Uitterlinden, Andre G. Wareham, Nicholas J. Gudnason, Vilmundur Rotter, Jerome I. Rettig, Rainer Uda, Manuela Strachan, David P. Witteman, Jacqueline C. M. Hartikainen, Anna-Liisa Beckmann, Jacques S. Boerwinkle, Eric Vasan, Ramachandran S. Boehnke, Michael Larson, Martin G. Jarvelin, Marjo-Riitta Psaty, Bruce M. Abecasis, Goncalo R. Chakravarti, Aravinda Elliott, Paul van Duijn, Cornelia M. Newton-Cheh, Christopher Levy, Daniel Caulfield, Mark J. Johnson, Toby Ehret, Georg B. Munroe, Patricia B. Rice, Kenneth M. Bochud, Murielle Johnson, Andrew D. Chasman, Daniel I. Smith, Albert V. Tobin, Martin D. Verwoert, Germaine C. Hwang, Shih-Jen Pihur, Vasyl Vollenweider, Peter O'Reilly, Paul F. Amin, Najaf Bragg-Gresham, Jennifer L. Teumer, Alexander Glazer, Nicole L. Launer, Lenore Zhao, Jing Hua Aulchenko, Yurii Heath, Simon Sober, Siim Parsa, Afshin Luan, Jian'an Arora, Pankaj Dehghan, Abbas Zhang, Feng Lucas, Gavin Hicks, Andrew A. Jackson, Anne U. Peden, John F. Tanaka, Toshiko Wild, Sarah H. Rudan, Igor Igl, Wilmar Milaneschi, Yuri Parker, Alex N. Fava, Cristiano Chambers, John C. Fox, Ervin R. Kumari, Meena Go, Min Jin van der Harst, Pim Kao, Wen Hong Linda Sjogren, Marketa Vinay, D. G. Alexander, Myriam Tabara, Yasuharu Shaw-Hawkins, Sue Whincup, Peter H. Liu, Yongmei Shi, Gang Kuusisto, Johanna Tayo, Bamidele Seielstad, Mark Sim, Xueling Nguyen, Khanh-Dung Hoang Lehtimaki, Terho Matullo, Giuseppe Wu, Ying Gaunt, Tom R. Onland-Moret, N. Charlotte Cooper, Matthew N. Platou, Carl G. P. Org, Elin Hardy, Rebecca Dahgam, Santosh Palmen, Jutta Vitart, Veronique Braund, Peter S. Kuznetsova, Tatiana Uiterwaal, Cuno S. P. M. Adeyemo, Adebowale Palmas, Walter Campbell, Harry Ludwig, Barbara Tomaszewski, Maciej Tzoulaki, Ioanna Palmer, Nicholette D. Aspelund, Thor Garcia, Melissa Chang, Yen-Pei C. O'Connell, Jeffrey R. Steinle, Nanette I. Grobbee, Diederick E. Arking, Dan E. Kardia, Sharon L. Morrison, Alanna C. Hernandez, Dena Najjar, Samer McArdle, Wendy L. Hadley, David Brown, Morris J. Connell, John M. Hingorani, Aroon D. Day, Ian N. M. Lawlor, Debbie A. Beilby, John P. Lawrence, Robert W. Clarke, Robert Hopewell, Jemma C. Ongen, Halit Dreisbach, Albert W. Li, Yali Young, J. Hunter Bis, Joshua C. Kahonen, Mika Viikari, Jorma Adair, Linda S. Lee, Nanette R. Chen, Ming-Huei Olden, Matthias Pattaro, Cristian Bolton, Judith A. Hoffman Koettgen, Anna Bergmann, Sven Mooser, Vincent Chaturvedi, Nish Frayling, Timothy M. Islam, Muhammad Jafar, Tazeen H. Erdmann, Jeanette Kulkarni, Smita R. Bornstein, Stefan R. Graessler, Juergen Groop, Leif Voight, Benjamin F. Kettunen, Johannes Howard, Philip Taylor, Andrew Guarrera, Simonetta Ricceri, Fulvio Emilsson, Valur Plump, Andrew Barroso, Ine S. Khaw, Kay-Tee Weder, Alan B. Hunt, Steven C. Sun, Yan V. Bergman, Richard N. Collins, Francis S. Bonnycastle, Lori L. Scott, Laura J. Stringham, Heather M. Peltonen, Leena Perola, Markus Vartiainen, Erkki Brand, Stefan-Martin Staessen, Jan A. Wang, Thomas J. Burton, Paul R. Artigas, Maria Soler Dong, Yanbin Snieder, Harold Wang, Xiaoling Zhu, Haidong Lohman, Kurt K. Rudock, Megan E. Heckbert, Susan R. Smith, Nicholas L. Wiggins, Kerri L. Doumatey, Ayo Shriner, Daniel Veldre, Gudrun Viigimaa, Margus Kinra, Sanjay Prabhakaran, Dorairaj Tripathy, Vikal Langefeld, Carl D. Rosengren, Annika Thelle, Dag S. Corsi, Anna Maria Singleton, Andrew Forrester, Terrence Hilton, Gina McKenzie, Colin A. Salako, Tunde Iwai, Naoharu Kita, Yoshikuni Ogihara, Toshio Ohkubo, Takayoshi Okamura, Tomonori Ueshima, Hirotsugu Umemura, Satoshi Eyheramendy, Susana Meitinger, Thomas Wichmann, H. -Erich Cho, Yoon Shin Kim, Hyung-Lae Lee, Jong-Young Scott, James Sehmi, Joban S. Zhang, Weihua Hedblad, Bo Nilsson, Peter Smith, George Davey Wong, Andrew Narisu, Narisu Stancakova, Alena Raffel, Leslie J. Yao, Jie Kathiresan, Sekar O'Donnell, Christopher J. Schwartz, Stephen M. Ikram, M. Arfan Longstreth, W. T., Jr. Mosley, Thomas H. Seshadri, Sudha Shrine, Nick R. G. Wain, Louise V. Morken, Mario A. Swift, Amy J. Laitinen, Jaana Prokopenko, Inga Zitting, Paavo Cooper, Jackie A. Humphries, Steve E. Danesh, John Rasheed, Asif Goel, Anuj Hamsten, Anders Watkins, Hugh Bakker, Stephan J. L. van Gilst, Wiek H. Janipalli, Charles S. Mani, K. Radha Yajnik, Chittaranjan S. Hofman, Albert Mattace-Raso, Francesco U. S. Oostra, Ben A. Demirkan, Ayse Isaacs, Aaron Rivadeneira, Fernando Lakatta, Edward G. Orru, Marco Scuteri, Angelo Ala-Korpela, Mika Kangas, Antti J. Lyytikainen, Leo-Pekka Soininen, Pasi Tukiainen, Taru Wurtz, Peter Ong, Rick Twee-Hee Doerr, Marcus Kroemer, Heyo K. Voelker, Uwe Voelzke, Henry Galan, Pilar Hercberg, Serge Lathrop, Mark Zelenika, Diana Deloukas, Panos Mangino, Massimo Spector, Tim D. Zhai, Guangju Meschia, James F. Nalls, Michael A. Sharma, Pankaj Terzic, Janos Kumar, M. V. Kranthi Denniff, Matthew Zukowska-Szczechowska, Ewa Wagenknecht, Lynne E. Fowkes, F. Gerald R. Charchar, Fadi J. Schwarz, Peter E. H. Hayward, Caroline Guo, Xiuqing Rotimi, Charles Bots, Michiel L. Brand, Eva Samani, Nilesh J. Polasek, Ozren Talmud, Philippa J. Nyberg, Fredrik Kuh, Diana Laan, Maris Hveem, Kristian Palmer, Lyle J. van der Schouw, Yvonne T. Casas, Juan P. Mohlke, Karen L. Vineis, Paolo Raitakari, Olli Ganesh, Santhi K. Wong, Tien Y. Tai, E. Shyong Cooper, Richard S. Laakso, Markku Rao, Dabeeru C. Harris, Tamara B. Morris, Richard W. Dominiczak, Anna F. Kivimaki, Mika Marmot, Michael G. Miki, Tetsuro Saleheen, Danish Chandak, Giriraj R. Coresh, Josef Navis, Gerjan Salomaa, Veikko Han, Bok-Ghee Zhu, Xiaofeng Kooner, Jaspal S. Melander, Olle Ridker, Paul M. Bandinelli, Stefania Gyllensten, Ulf B. Wright, Alan F. Wilson, James F. Ferrucci, Luigi Farrall, Martin Tuomilehto, Jaakko Pramstaller, Peter P. Elosua, Roberto Soranzo, Nicole Sijbrands, Eric J. G. Altshuler, David Loos, Ruth J. F. Shuldiner, Alan R. Gieger, Christian Meneton, Pierre Uitterlinden, Andre G. Wareham, Nicholas J. Gudnason, Vilmundur Rotter, Jerome I. Rettig, Rainer Uda, Manuela Strachan, David P. Witteman, Jacqueline C. M. Hartikainen, Anna-Liisa Beckmann, Jacques S. Boerwinkle, Eric Vasan, Ramachandran S. Boehnke, Michael Larson, Martin G. Jarvelin, Marjo-Riitta Psaty, Bruce M. Abecasis, Goncalo R. Chakravarti, Aravinda Elliott, Paul van Duijn, Cornelia M. Newton-Cheh, Christopher Levy, Daniel Caulfield, Mark J. Johnson, Toby
Publication Year :
2011
Abstract
Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). 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.
Details
Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1235080793
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1038.nature10405