Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~19...

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Main Authors:	Surendran, Praveen, Drenos, Fotios, Young, Robin, Warren, Helen, Cook, James P, Manning, Alisa K, Grarup, Niels, Sim, Xueling, Barnes, Daniel R, Witkowska, Kate, Staley, James R, Tragante, Vinicius, Tukiainen, Taru, Yaghootkar, Hanieh, Masca, Nicholas, Freitag, Daniel F, Ferreira, Teresa, Giannakopoulou, Olga, Tinker, Andrew, Harakalova, Magdalena, Mihailov, Evelin, Liu, Chunyu, Kraja, Aldi T, Fallgaard Nielsen, Sune, Rasheed, Asif, Samuel, Maria, Zhao, Wei, Bonnycastle, Lori L, Jackson, Anne U, Narisu, Narisu, Swift, Amy J, Southam, Lorraine, Marten, Jonathan, Huyghe, Jeroen R, Stančáková, Alena, Fava, Cristiano, Ohlsson, Therese, Matchan, Angela, Stirrups, Kathleen E, Bork-Jensen, Jette, Gjesing, Anette P, Kontto, Jukka, Perola, Markus, Shaw-Hawkins, Susan, Havulinna, Aki S, Zhang, He, Donnelly, Louise A, Groves, Christopher J, Rayner, N William, Neville, Matt J, Robertson, Neil R, Yiorkas, Andrianos M, Herzig, Karl-Heinz, Kajantie, Eero, Zhang, Weihua, Willems, Sara M, Lannfelt, Lars, Malerba, Giovanni, Soranzo, Nicole, Trabetti, Elisabetta, Verweij, Niek, Evangelou, Evangelos, Moayyeri, Alireza, Vergnaud, Anne-Claire, Nelson, Christopher P, Poveda, Alaitz, Varga, Tibor V, Caslake, Muriel, de Craen, Anton JM, Trompet, Stella, Luan, Jian’an, Scott, Robert A, Harris, Sarah E, Liewald, David CM, Marioni, Riccardo, Menni, Cristina, Farmaki, Aliki-Eleni, Hallmans, Göran, Renström, Frida, Huffman, Jennifer E, Hassinen, Maija, Burgess, Stephen, Vasan, Ramachandran S, Felix, Janine F, Uria-Nickelsen, Maria, Malarstig, Anders, Reily, Dermot F, Hoek, Maarten, Vogt, Thomas, Lin, Honghuang, Lieb, Wolfgang, Traylor, Matthew, Markus, Hugh F, Highland, Heather M, Justice, Anne E, Marouli, Eirini, Lindström, Jaana, Uusitupa, Matti, Komulainen, Pirjo, Lakka, Timo A, Rauramaa, Rainer, Polasek, Ozren, Rudan, Igor, Rolandsson, Olov, Franks, Paul W, Dedoussis, George, Spector, Timothy D, Jousilahti, Pekka, Männistö, Satu, Deary, Ian J, Starr, John M, Langenberg, Claudia, Wareham, Nick J, Brown, Morris J, Dominiczak, Anna F, Connell, John M, Jukema, J Wouter, Sattar, Naveed, Ford, Ian, Packard, Chris J, Esko, Tõnu, Mägi, Reedik, Metspalu, Andres, de Boer, Rudolf A, van der Meer, Peter, van der Harst, Pim, Gambaro, Giovanni, Ingelsson, Erik, Lind, Lars, de Bakker, Paul IW, Numans, Mattijs E, Brandslund, Ivan, Christensen, Cramer, Petersen, Eva RB, Korpi-Hyövälti, Eeva, Oksa, Heikki, Chambers, John C, Kooner, Jaspal S, Blakemore, Alexandra IF, Franks, Steve, Jarvelin, Marjo-Riitta, Husemoen, Lise L, Linneberg, Allan, Skaaby, Tea, Thuesen, Betina, Karpe, Fredrik, Tuomilehto, Jaakko, Doney, Alex SF, Morris, Andrew D, Palmer, Colin NA, Holmen, Oddgeir Lingaas, Hveem, Kristian, Willer, Cristen J, Tuomi, Tiinamaija, Groop, Leif, Käräjämäki, AnneMari, Palotie, Aarno, Ripatti, Samuli, Salomaa, Veikko, Alam, Dewan S, Shafi Majumder, Abdulla al, Di Angelantonio, Emanuele, Chowdhury, Rajiv, McCarthy, Mark I, Poulter, Neil, Stanton, Alice V, Sever, Peter, Amouyel, Philippe, Arveiler, Dominique, Blankenberg, Stefan, Ferrières, Jean, Kee, Frank, Kuulasmaa, Kari, Müller-Nurasyid, Martina, Veronesi, Giovanni, Virtamo, Jarmo, Deloukas, Panos, Elliott, Paul, Zeggini, Eleftheria, Kathiresan, Sekar, Melander, Olle, Kuusisto, Johanna, Laakso, Markku, Padmanabhan, Sandosh, Porteous, David, Hayward, Caroline, Scotland, Generation, Collins, Francis S, Mohlke, Karen L, Hansen, Torben, Pedersen, Oluf, Boehnke, Michael, Stringham, Heather M, Frossard, Philippe, Newton-Cheh, Christopher, Tobin, Martin D, Nordestgaard, Børge Grønne, Caulfield, Mark J, Mahajan, Anubha, Morris, Andrew P, Tomaszewski, Maciej, Samani, Nilesh J, Saleheen, Danish, Asselbergs, Folkert W, Lindgren, Cecilia M, Danesh, John, Wain, Louise V, Butterworth, Adam S, Howson, Joanna MM, Munroe, Patricia B
Format:	Online
Language:	English
Published:	2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056636/

id	pubmed-5056636
recordtype	oai_dc
spelling	pubmed-50566362017-03-12 Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension Surendran, Praveen Drenos, Fotios Young, Robin Warren, Helen Cook, James P Manning, Alisa K Grarup, Niels Sim, Xueling Barnes, Daniel R Witkowska, Kate Staley, James R Tragante, Vinicius Tukiainen, Taru Yaghootkar, Hanieh Masca, Nicholas Freitag, Daniel F Ferreira, Teresa Giannakopoulou, Olga Tinker, Andrew Harakalova, Magdalena Mihailov, Evelin Liu, Chunyu Kraja, Aldi T Fallgaard Nielsen, Sune Rasheed, Asif Samuel, Maria Zhao, Wei Bonnycastle, Lori L Jackson, Anne U Narisu, Narisu Swift, Amy J Southam, Lorraine Marten, Jonathan Huyghe, Jeroen R Stančáková, Alena Fava, Cristiano Ohlsson, Therese Matchan, Angela Stirrups, Kathleen E Bork-Jensen, Jette Gjesing, Anette P Kontto, Jukka Perola, Markus Shaw-Hawkins, Susan Havulinna, Aki S Zhang, He Donnelly, Louise A Groves, Christopher J Rayner, N William Neville, Matt J Robertson, Neil R Yiorkas, Andrianos M Herzig, Karl-Heinz Kajantie, Eero Zhang, Weihua Willems, Sara M Lannfelt, Lars Malerba, Giovanni Soranzo, Nicole Trabetti, Elisabetta Verweij, Niek Evangelou, Evangelos Moayyeri, Alireza Vergnaud, Anne-Claire Nelson, Christopher P Poveda, Alaitz Varga, Tibor V Caslake, Muriel de Craen, Anton JM Trompet, Stella Luan, Jian’an Scott, Robert A Harris, Sarah E Liewald, David CM Marioni, Riccardo Menni, Cristina Farmaki, Aliki-Eleni Hallmans, Göran Renström, Frida Huffman, Jennifer E Hassinen, Maija Burgess, Stephen Vasan, Ramachandran S Felix, Janine F Uria-Nickelsen, Maria Malarstig, Anders Reily, Dermot F Hoek, Maarten Vogt, Thomas Lin, Honghuang Lieb, Wolfgang Traylor, Matthew Markus, Hugh F Highland, Heather M Justice, Anne E Marouli, Eirini Lindström, Jaana Uusitupa, Matti Komulainen, Pirjo Lakka, Timo A Rauramaa, Rainer Polasek, Ozren Rudan, Igor Rolandsson, Olov Franks, Paul W Dedoussis, George Spector, Timothy D Jousilahti, Pekka Männistö, Satu Deary, Ian J Starr, John M Langenberg, Claudia Wareham, Nick J Brown, Morris J Dominiczak, Anna F Connell, John M Jukema, J Wouter Sattar, Naveed Ford, Ian Packard, Chris J Esko, Tõnu Mägi, Reedik Metspalu, Andres de Boer, Rudolf A van der Meer, Peter van der Harst, Pim Gambaro, Giovanni Ingelsson, Erik Lind, Lars de Bakker, Paul IW Numans, Mattijs E Brandslund, Ivan Christensen, Cramer Petersen, Eva RB Korpi-Hyövälti, Eeva Oksa, Heikki Chambers, John C Kooner, Jaspal S Blakemore, Alexandra IF Franks, Steve Jarvelin, Marjo-Riitta Husemoen, Lise L Linneberg, Allan Skaaby, Tea Thuesen, Betina Karpe, Fredrik Tuomilehto, Jaakko Doney, Alex SF Morris, Andrew D Palmer, Colin NA Holmen, Oddgeir Lingaas Hveem, Kristian Willer, Cristen J Tuomi, Tiinamaija Groop, Leif Käräjämäki, AnneMari Palotie, Aarno Ripatti, Samuli Salomaa, Veikko Alam, Dewan S Shafi Majumder, Abdulla al Di Angelantonio, Emanuele Chowdhury, Rajiv McCarthy, Mark I Poulter, Neil Stanton, Alice V Sever, Peter Amouyel, Philippe Arveiler, Dominique Blankenberg, Stefan Ferrières, Jean Kee, Frank Kuulasmaa, Kari Müller-Nurasyid, Martina Veronesi, Giovanni Virtamo, Jarmo Deloukas, Panos Elliott, Paul Zeggini, Eleftheria Kathiresan, Sekar Melander, Olle Kuusisto, Johanna Laakso, Markku Padmanabhan, Sandosh Porteous, David Hayward, Caroline Scotland, Generation Collins, Francis S Mohlke, Karen L Hansen, Torben Pedersen, Oluf Boehnke, Michael Stringham, Heather M Frossard, Philippe Newton-Cheh, Christopher Tobin, Martin D Nordestgaard, Børge Grønne Caulfield, Mark J Mahajan, Anubha Morris, Andrew P Tomaszewski, Maciej Samani, Nilesh J Saleheen, Danish Asselbergs, Folkert W Lindgren, Cecilia M Danesh, John Wain, Louise V Butterworth, Adam S Howson, Joanna MM Munroe, Patricia B Article High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in A2ML1 and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention. 2016-09-12 2016-10 /pmc/articles/PMC5056636/ /pubmed/27618447 http://dx.doi.org/10.1038/ng.3654 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Surendran, Praveen Drenos, Fotios Young, Robin Warren, Helen Cook, James P Manning, Alisa K Grarup, Niels Sim, Xueling Barnes, Daniel R Witkowska, Kate Staley, James R Tragante, Vinicius Tukiainen, Taru Yaghootkar, Hanieh Masca, Nicholas Freitag, Daniel F Ferreira, Teresa Giannakopoulou, Olga Tinker, Andrew Harakalova, Magdalena Mihailov, Evelin Liu, Chunyu Kraja, Aldi T Fallgaard Nielsen, Sune Rasheed, Asif Samuel, Maria Zhao, Wei Bonnycastle, Lori L Jackson, Anne U Narisu, Narisu Swift, Amy J Southam, Lorraine Marten, Jonathan Huyghe, Jeroen R Stančáková, Alena Fava, Cristiano Ohlsson, Therese Matchan, Angela Stirrups, Kathleen E Bork-Jensen, Jette Gjesing, Anette P Kontto, Jukka Perola, Markus Shaw-Hawkins, Susan Havulinna, Aki S Zhang, He Donnelly, Louise A Groves, Christopher J Rayner, N William Neville, Matt J Robertson, Neil R Yiorkas, Andrianos M Herzig, Karl-Heinz Kajantie, Eero Zhang, Weihua Willems, Sara M Lannfelt, Lars Malerba, Giovanni Soranzo, Nicole Trabetti, Elisabetta Verweij, Niek Evangelou, Evangelos Moayyeri, Alireza Vergnaud, Anne-Claire Nelson, Christopher P Poveda, Alaitz Varga, Tibor V Caslake, Muriel de Craen, Anton JM Trompet, Stella Luan, Jian’an Scott, Robert A Harris, Sarah E Liewald, David CM Marioni, Riccardo Menni, Cristina Farmaki, Aliki-Eleni Hallmans, Göran Renström, Frida Huffman, Jennifer E Hassinen, Maija Burgess, Stephen Vasan, Ramachandran S Felix, Janine F Uria-Nickelsen, Maria Malarstig, Anders Reily, Dermot F Hoek, Maarten Vogt, Thomas Lin, Honghuang Lieb, Wolfgang Traylor, Matthew Markus, Hugh F Highland, Heather M Justice, Anne E Marouli, Eirini Lindström, Jaana Uusitupa, Matti Komulainen, Pirjo Lakka, Timo A Rauramaa, Rainer Polasek, Ozren Rudan, Igor Rolandsson, Olov Franks, Paul W Dedoussis, George Spector, Timothy D Jousilahti, Pekka Männistö, Satu Deary, Ian J Starr, John M Langenberg, Claudia Wareham, Nick J Brown, Morris J Dominiczak, Anna F Connell, John M Jukema, J Wouter Sattar, Naveed Ford, Ian Packard, Chris J Esko, Tõnu Mägi, Reedik Metspalu, Andres de Boer, Rudolf A van der Meer, Peter van der Harst, Pim Gambaro, Giovanni Ingelsson, Erik Lind, Lars de Bakker, Paul IW Numans, Mattijs E Brandslund, Ivan Christensen, Cramer Petersen, Eva RB Korpi-Hyövälti, Eeva Oksa, Heikki Chambers, John C Kooner, Jaspal S Blakemore, Alexandra IF Franks, Steve Jarvelin, Marjo-Riitta Husemoen, Lise L Linneberg, Allan Skaaby, Tea Thuesen, Betina Karpe, Fredrik Tuomilehto, Jaakko Doney, Alex SF Morris, Andrew D Palmer, Colin NA Holmen, Oddgeir Lingaas Hveem, Kristian Willer, Cristen J Tuomi, Tiinamaija Groop, Leif Käräjämäki, AnneMari Palotie, Aarno Ripatti, Samuli Salomaa, Veikko Alam, Dewan S Shafi Majumder, Abdulla al Di Angelantonio, Emanuele Chowdhury, Rajiv McCarthy, Mark I Poulter, Neil Stanton, Alice V Sever, Peter Amouyel, Philippe Arveiler, Dominique Blankenberg, Stefan Ferrières, Jean Kee, Frank Kuulasmaa, Kari Müller-Nurasyid, Martina Veronesi, Giovanni Virtamo, Jarmo Deloukas, Panos Elliott, Paul Zeggini, Eleftheria Kathiresan, Sekar Melander, Olle Kuusisto, Johanna Laakso, Markku Padmanabhan, Sandosh Porteous, David Hayward, Caroline Scotland, Generation Collins, Francis S Mohlke, Karen L Hansen, Torben Pedersen, Oluf Boehnke, Michael Stringham, Heather M Frossard, Philippe Newton-Cheh, Christopher Tobin, Martin D Nordestgaard, Børge Grønne Caulfield, Mark J Mahajan, Anubha Morris, Andrew P Tomaszewski, Maciej Samani, Nilesh J Saleheen, Danish Asselbergs, Folkert W Lindgren, Cecilia M Danesh, John Wain, Louise V Butterworth, Adam S Howson, Joanna MM Munroe, Patricia B
spellingShingle	Surendran, Praveen Drenos, Fotios Young, Robin Warren, Helen Cook, James P Manning, Alisa K Grarup, Niels Sim, Xueling Barnes, Daniel R Witkowska, Kate Staley, James R Tragante, Vinicius Tukiainen, Taru Yaghootkar, Hanieh Masca, Nicholas Freitag, Daniel F Ferreira, Teresa Giannakopoulou, Olga Tinker, Andrew Harakalova, Magdalena Mihailov, Evelin Liu, Chunyu Kraja, Aldi T Fallgaard Nielsen, Sune Rasheed, Asif Samuel, Maria Zhao, Wei Bonnycastle, Lori L Jackson, Anne U Narisu, Narisu Swift, Amy J Southam, Lorraine Marten, Jonathan Huyghe, Jeroen R Stančáková, Alena Fava, Cristiano Ohlsson, Therese Matchan, Angela Stirrups, Kathleen E Bork-Jensen, Jette Gjesing, Anette P Kontto, Jukka Perola, Markus Shaw-Hawkins, Susan Havulinna, Aki S Zhang, He Donnelly, Louise A Groves, Christopher J Rayner, N William Neville, Matt J Robertson, Neil R Yiorkas, Andrianos M Herzig, Karl-Heinz Kajantie, Eero Zhang, Weihua Willems, Sara M Lannfelt, Lars Malerba, Giovanni Soranzo, Nicole Trabetti, Elisabetta Verweij, Niek Evangelou, Evangelos Moayyeri, Alireza Vergnaud, Anne-Claire Nelson, Christopher P Poveda, Alaitz Varga, Tibor V Caslake, Muriel de Craen, Anton JM Trompet, Stella Luan, Jian’an Scott, Robert A Harris, Sarah E Liewald, David CM Marioni, Riccardo Menni, Cristina Farmaki, Aliki-Eleni Hallmans, Göran Renström, Frida Huffman, Jennifer E Hassinen, Maija Burgess, Stephen Vasan, Ramachandran S Felix, Janine F Uria-Nickelsen, Maria Malarstig, Anders Reily, Dermot F Hoek, Maarten Vogt, Thomas Lin, Honghuang Lieb, Wolfgang Traylor, Matthew Markus, Hugh F Highland, Heather M Justice, Anne E Marouli, Eirini Lindström, Jaana Uusitupa, Matti Komulainen, Pirjo Lakka, Timo A Rauramaa, Rainer Polasek, Ozren Rudan, Igor Rolandsson, Olov Franks, Paul W Dedoussis, George Spector, Timothy D Jousilahti, Pekka Männistö, Satu Deary, Ian J Starr, John M Langenberg, Claudia Wareham, Nick J Brown, Morris J Dominiczak, Anna F Connell, John M Jukema, J Wouter Sattar, Naveed Ford, Ian Packard, Chris J Esko, Tõnu Mägi, Reedik Metspalu, Andres de Boer, Rudolf A van der Meer, Peter van der Harst, Pim Gambaro, Giovanni Ingelsson, Erik Lind, Lars de Bakker, Paul IW Numans, Mattijs E Brandslund, Ivan Christensen, Cramer Petersen, Eva RB Korpi-Hyövälti, Eeva Oksa, Heikki Chambers, John C Kooner, Jaspal S Blakemore, Alexandra IF Franks, Steve Jarvelin, Marjo-Riitta Husemoen, Lise L Linneberg, Allan Skaaby, Tea Thuesen, Betina Karpe, Fredrik Tuomilehto, Jaakko Doney, Alex SF Morris, Andrew D Palmer, Colin NA Holmen, Oddgeir Lingaas Hveem, Kristian Willer, Cristen J Tuomi, Tiinamaija Groop, Leif Käräjämäki, AnneMari Palotie, Aarno Ripatti, Samuli Salomaa, Veikko Alam, Dewan S Shafi Majumder, Abdulla al Di Angelantonio, Emanuele Chowdhury, Rajiv McCarthy, Mark I Poulter, Neil Stanton, Alice V Sever, Peter Amouyel, Philippe Arveiler, Dominique Blankenberg, Stefan Ferrières, Jean Kee, Frank Kuulasmaa, Kari Müller-Nurasyid, Martina Veronesi, Giovanni Virtamo, Jarmo Deloukas, Panos Elliott, Paul Zeggini, Eleftheria Kathiresan, Sekar Melander, Olle Kuusisto, Johanna Laakso, Markku Padmanabhan, Sandosh Porteous, David Hayward, Caroline Scotland, Generation Collins, Francis S Mohlke, Karen L Hansen, Torben Pedersen, Oluf Boehnke, Michael Stringham, Heather M Frossard, Philippe Newton-Cheh, Christopher Tobin, Martin D Nordestgaard, Børge Grønne Caulfield, Mark J Mahajan, Anubha Morris, Andrew P Tomaszewski, Maciej Samani, Nilesh J Saleheen, Danish Asselbergs, Folkert W Lindgren, Cecilia M Danesh, John Wain, Louise V Butterworth, Adam S Howson, Joanna MM Munroe, Patricia B Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
author_facet	Surendran, Praveen Drenos, Fotios Young, Robin Warren, Helen Cook, James P Manning, Alisa K Grarup, Niels Sim, Xueling Barnes, Daniel R Witkowska, Kate Staley, James R Tragante, Vinicius Tukiainen, Taru Yaghootkar, Hanieh Masca, Nicholas Freitag, Daniel F Ferreira, Teresa Giannakopoulou, Olga Tinker, Andrew Harakalova, Magdalena Mihailov, Evelin Liu, Chunyu Kraja, Aldi T Fallgaard Nielsen, Sune Rasheed, Asif Samuel, Maria Zhao, Wei Bonnycastle, Lori L Jackson, Anne U Narisu, Narisu Swift, Amy J Southam, Lorraine Marten, Jonathan Huyghe, Jeroen R Stančáková, Alena Fava, Cristiano Ohlsson, Therese Matchan, Angela Stirrups, Kathleen E Bork-Jensen, Jette Gjesing, Anette P Kontto, Jukka Perola, Markus Shaw-Hawkins, Susan Havulinna, Aki S Zhang, He Donnelly, Louise A Groves, Christopher J Rayner, N William Neville, Matt J Robertson, Neil R Yiorkas, Andrianos M Herzig, Karl-Heinz Kajantie, Eero Zhang, Weihua Willems, Sara M Lannfelt, Lars Malerba, Giovanni Soranzo, Nicole Trabetti, Elisabetta Verweij, Niek Evangelou, Evangelos Moayyeri, Alireza Vergnaud, Anne-Claire Nelson, Christopher P Poveda, Alaitz Varga, Tibor V Caslake, Muriel de Craen, Anton JM Trompet, Stella Luan, Jian’an Scott, Robert A Harris, Sarah E Liewald, David CM Marioni, Riccardo Menni, Cristina Farmaki, Aliki-Eleni Hallmans, Göran Renström, Frida Huffman, Jennifer E Hassinen, Maija Burgess, Stephen Vasan, Ramachandran S Felix, Janine F Uria-Nickelsen, Maria Malarstig, Anders Reily, Dermot F Hoek, Maarten Vogt, Thomas Lin, Honghuang Lieb, Wolfgang Traylor, Matthew Markus, Hugh F Highland, Heather M Justice, Anne E Marouli, Eirini Lindström, Jaana Uusitupa, Matti Komulainen, Pirjo Lakka, Timo A Rauramaa, Rainer Polasek, Ozren Rudan, Igor Rolandsson, Olov Franks, Paul W Dedoussis, George Spector, Timothy D Jousilahti, Pekka Männistö, Satu Deary, Ian J Starr, John M Langenberg, Claudia Wareham, Nick J Brown, Morris J Dominiczak, Anna F Connell, John M Jukema, J Wouter Sattar, Naveed Ford, Ian Packard, Chris J Esko, Tõnu Mägi, Reedik Metspalu, Andres de Boer, Rudolf A van der Meer, Peter van der Harst, Pim Gambaro, Giovanni Ingelsson, Erik Lind, Lars de Bakker, Paul IW Numans, Mattijs E Brandslund, Ivan Christensen, Cramer Petersen, Eva RB Korpi-Hyövälti, Eeva Oksa, Heikki Chambers, John C Kooner, Jaspal S Blakemore, Alexandra IF Franks, Steve Jarvelin, Marjo-Riitta Husemoen, Lise L Linneberg, Allan Skaaby, Tea Thuesen, Betina Karpe, Fredrik Tuomilehto, Jaakko Doney, Alex SF Morris, Andrew D Palmer, Colin NA Holmen, Oddgeir Lingaas Hveem, Kristian Willer, Cristen J Tuomi, Tiinamaija Groop, Leif Käräjämäki, AnneMari Palotie, Aarno Ripatti, Samuli Salomaa, Veikko Alam, Dewan S Shafi Majumder, Abdulla al Di Angelantonio, Emanuele Chowdhury, Rajiv McCarthy, Mark I Poulter, Neil Stanton, Alice V Sever, Peter Amouyel, Philippe Arveiler, Dominique Blankenberg, Stefan Ferrières, Jean Kee, Frank Kuulasmaa, Kari Müller-Nurasyid, Martina Veronesi, Giovanni Virtamo, Jarmo Deloukas, Panos Elliott, Paul Zeggini, Eleftheria Kathiresan, Sekar Melander, Olle Kuusisto, Johanna Laakso, Markku Padmanabhan, Sandosh Porteous, David Hayward, Caroline Scotland, Generation Collins, Francis S Mohlke, Karen L Hansen, Torben Pedersen, Oluf Boehnke, Michael Stringham, Heather M Frossard, Philippe Newton-Cheh, Christopher Tobin, Martin D Nordestgaard, Børge Grønne Caulfield, Mark J Mahajan, Anubha Morris, Andrew P Tomaszewski, Maciej Samani, Nilesh J Saleheen, Danish Asselbergs, Folkert W Lindgren, Cecilia M Danesh, John Wain, Louise V Butterworth, Adam S Howson, Joanna MM Munroe, Patricia B
author_sort	Surendran, Praveen
title	Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
title_short	Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
title_full	Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
title_fullStr	Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
title_full_unstemmed	Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
title_sort	trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
description	High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in A2ML1 and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056636/
_version_	1613678091572346880

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

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