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

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

doi:10.1038/ng.3654

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

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

Division of Cardiology

Research output: Contribution to journal › Article › peer-review

183 Scopus citations

Abstract

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 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/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.

Original language	English
Pages (from-to)	1151-1161
Number of pages	11
Journal	Nature Genetics
Volume	48
Issue number	10
DOIs	https://doi.org/10.1038/ng.3654
State	Published - Oct 1 2016

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10.1038/ng.3654

Cite this

Surendran, P., Drenos, F., Young, R., Warren, H., Cook, J. P., Manning, A. K., Grarup, N., Sim, X., Barnes, D. R., Witkowska, K., Staley, J. R., Tragante, V., Tukiainen, T., Yaghootkar, H., Masca, N., Freitag, D. F., Ferreira, T., Giannakopoulou, O., Tinker, A., ... Munroe, P. B. (2016). Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. Nature Genetics, 48(10), 1151-1161. https://doi.org/10.1038/ng.3654

@article{174990b9a6fb4437aa3970bb062f0927,

title = "Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension",

abstract = "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 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/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.",

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

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Surendran, P, Drenos, F, Young, R, Warren, H, Cook, JP, Manning, AK, Grarup, N, Sim, X, Barnes, DR, Witkowska, K, Staley, JR, Tragante, V, Tukiainen, T, Yaghootkar, H, Masca, N, Freitag, DF, Ferreira, T, Giannakopoulou, O, Tinker, A, Harakalova, M, Mihailov, E, Liu, C, Kraja, AT, Nielsen, SF, Rasheed, A, Samuel, M, Zhao, W, Bonnycastle, LL, Jackson, AU, Narisu, N, Swift, AJ, Southam, L, Marten, J, Huyghe, JR, Stančáková, A, Fava, C, Ohlsson, T, Matchan, A, Stirrups, KE, Bork-Jensen, J, Gjesing, AP, Kontto, J, Perola, M, Shaw-Hawkins, S, Havulinna, AS, Zhang, H, Donnelly, LA, Groves, CJ, Rayner, NW, Neville, MJ, Robertson, NR, Yiorkas, AM, Herzig, KH, Kajantie, E, Zhang, W, Willems, SM, Lannfelt, L, Malerba, G, Soranzo, N, Trabetti, E, Verweij, N, Evangelou, E, Moayyeri, A, Vergnaud, AC, Nelson, CP, Poveda, A, Varga, TV, Caslake, M, De Craen, AJM, Trompet, S, Luan, JA, Scott, RA, Harris, SE, Liewald, DCM, Marioni, R, Menni, C, Farmaki, AE, Hallmans, G, Renström, F, Huffman, JE, Hassinen, M, Burgess, S, Vasan, RS, Felix, JF, Uria-Nickelsen, M, Malarstig, A, Reilly, DF, Hoek, M, Vogt, TF, Lin, H, Lieb, W, Traylor, M, Markus, HS, Highland, HM, Justice, AE, Marouli, E, Lindström, J, Uusitupa, M, Komulainen, P, Lakka, TA, Rauramaa, R, Polasek, O, Rudan, I, Rolandsson, O, Franks, PW, Dedoussis, G, Spector, TD, Jousilahti, P, Männistö, S, Deary, IJ, Starr, JM, Langenberg, C, Wareham, NJ, Brown, MJ, Dominiczak, AF, Connell, JM, Jukema, JW, Sattar, N, Ford, I, Packard, CJ, Esko, T, Mägi, R, Metspalu, A, De Boer, RA, Van Der Meer, P, Van Der Harst, P, Gambaro, G, Ingelsson, E, Lind, L, De Bakker, PIW, Numans, ME, Brandslund, I, Christensen, C, Petersen, ERB, Korpi-Hyövälti, E, Oksa, H, Chambers, JC, Kooner, JS, Blakemore, AIF, Franks, S, Jarvelin, MR, Husemoen, LL, Linneberg, A, Skaaby, T, Thuesen, B, Karpe, F, Tuomilehto, J, Doney, ASF, Morris, AD, Palmer, CNA, Holmen, OL, Hveem, K, Willer, CJ, Tuomi, T, Groop, L, Käräjämäki, A, Palotie, A, Ripatti, S, Salomaa, V, Alam, DS, Majumder, AAS, Di Angelantonio, E, Chowdhury, R, McCarthy, MI, Poulter, N, Stanton, AV, Sever, P, Amouyel, P, Arveiler, D, Blankenberg, S, Ferrières, J, Kee, F, Kuulasmaa, K, Müller-Nurasyid, M, Veronesi, G, Virtamo, J, Deloukas, P, Elliott, P, Zeggini, E, Kathiresan, S, Melander, O, Kuusisto, J, Laakso, M, Padmanabhan, S, Porteous, DJ, Hayward, C, Scotland, G, Collins, FS, Mohlke, KL, Hansen, T, Pedersen, O, Boehnke, M, Stringham, HM, Frossard, P, Newton-Cheh, C, Tobin, MD, Nordestgaard, BG, Caulfield, MJ, Mahajan, A, Morris, AP, Tomaszewski, M, Samani, NJ, Saleheen, D, Asselbergs, FW, Lindgren, CM, Danesh, J, Wain, LV, Butterworth, AS, Howson, JMM & Munroe, PB 2016, 'Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension', Nature Genetics, vol. 48, no. 10, pp. 1151-1161. https://doi.org/10.1038/ng.3654

TY - JOUR

T1 - Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

AU - Surendran, Praveen

AU - Drenos, Fotios

AU - Young, Robin

AU - Warren, Helen

AU - Cook, James P.

AU - Manning, Alisa K.

AU - Grarup, Niels

AU - Sim, Xueling

AU - Barnes, Daniel R.

AU - Witkowska, Kate

AU - Staley, James R.

AU - Tragante, Vinicius

AU - Tukiainen, Taru

AU - Yaghootkar, Hanieh

AU - Masca, Nicholas

AU - Freitag, Daniel F.

AU - Ferreira, Teresa

AU - Giannakopoulou, Olga

AU - Tinker, Andrew

AU - Harakalova, Magdalena

AU - Mihailov, Evelin

AU - Liu, Chunyu

AU - Kraja, Aldi T.

AU - Nielsen, Sune Fallgaard

AU - Rasheed, Asif

AU - Samuel, Maria

AU - Zhao, Wei

AU - Bonnycastle, Lori L.

AU - Jackson, Anne U.

AU - Narisu, Narisu

AU - Swift, Amy J.

AU - Southam, Lorraine

AU - Marten, Jonathan

AU - Huyghe, Jeroen R.

AU - Stančáková, Alena

AU - Fava, Cristiano

AU - Ohlsson, Therese

AU - Matchan, Angela

AU - Stirrups, Kathleen E.

AU - Bork-Jensen, Jette

AU - Gjesing, Anette P.

AU - Kontto, Jukka

AU - Perola, Markus

AU - Shaw-Hawkins, Susan

AU - Havulinna, Aki S.

AU - Zhang, He

AU - Donnelly, Louise A.

AU - Groves, Christopher J.

AU - Rayner, N. William

AU - Neville, Matt J.

AU - Robertson, Neil R.

AU - Yiorkas, Andrianos M.

AU - Herzig, Karl Heinz

AU - Kajantie, Eero

AU - Zhang, Weihua

AU - Willems, Sara M.

AU - Lannfelt, Lars

AU - Malerba, Giovanni

AU - Soranzo, Nicole

AU - Trabetti, Elisabetta

AU - Verweij, Niek

AU - Evangelou, Evangelos

AU - Moayyeri, Alireza

AU - Vergnaud, Anne Claire

AU - Nelson, Christopher P.

AU - Poveda, Alaitz

AU - Varga, Tibor V.

AU - Caslake, Muriel

AU - De Craen, Anton J.M.

AU - Trompet, Stella

AU - Luan, Jian'An

AU - Scott, Robert A.

AU - Harris, Sarah E.

AU - Liewald, David C.M.

AU - Marioni, Riccardo

AU - Menni, Cristina

AU - Farmaki, Aliki Eleni

AU - Hallmans, Göran

AU - Renström, Frida

AU - Huffman, Jennifer E.

AU - Hassinen, Maija

AU - Burgess, Stephen

AU - Vasan, Ramachandran S.

AU - Felix, Janine F.

AU - Uria-Nickelsen, Maria

AU - Malarstig, Anders

AU - Reilly, Dermot F.

AU - Hoek, Maarten

AU - Vogt, Thomas F.

AU - Lin, Honghuang

AU - Lieb, Wolfgang

AU - Traylor, Matthew

AU - Markus, Hugh S.

AU - Highland, Heather M.

AU - Justice, Anne E.

AU - Marouli, Eirini

AU - Lindström, Jaana

AU - Uusitupa, Matti

AU - Komulainen, Pirjo

AU - Lakka, Timo A.

AU - Rauramaa, Rainer

AU - Polasek, Ozren

AU - Rudan, Igor

AU - Rolandsson, Olov

AU - Franks, Paul W.

AU - Dedoussis, George

AU - Spector, Timothy D.

AU - Jousilahti, Pekka

AU - Männistö, Satu

AU - Deary, Ian J.

AU - Starr, John M.

AU - Langenberg, Claudia

AU - Wareham, Nick J.

AU - Brown, Morris J.

AU - Dominiczak, Anna F.

AU - Connell, John M.

AU - Jukema, J. Wouter

AU - Sattar, Naveed

AU - Ford, Ian

AU - Packard, Chris J.

AU - Esko, Tõnu

AU - Mägi, Reedik

AU - Metspalu, Andres

AU - De Boer, Rudolf A.

AU - Van Der Meer, Peter

AU - Van Der Harst, Pim

AU - Gambaro, Giovanni

AU - Ingelsson, Erik

AU - Lind, Lars

AU - De Bakker, Paul I.W.

AU - Numans, Mattijs E.

AU - Brandslund, Ivan

AU - Christensen, Cramer

AU - Petersen, Eva R.B.

AU - Korpi-Hyövälti, Eeva

AU - Oksa, Heikki

AU - Chambers, John C.

AU - Kooner, Jaspal S.

AU - Blakemore, Alexandra I.F.

AU - Franks, Steve

AU - Jarvelin, Marjo Riitta

AU - Husemoen, Lise L.

AU - Linneberg, Allan

AU - Skaaby, Tea

AU - Thuesen, Betina

AU - Karpe, Fredrik

AU - Tuomilehto, Jaakko

AU - Doney, Alex S.F.

AU - Morris, Andrew D.

AU - Palmer, Colin N.A.

AU - Holmen, Oddgeir Lingaas

AU - Hveem, Kristian

AU - Willer, Cristen J.

AU - Tuomi, Tiinamaija

AU - Groop, Leif

AU - Käräjämäki, Annemari

AU - Palotie, Aarno

AU - Ripatti, Samuli

AU - Salomaa, Veikko

AU - Alam, Dewan S.

AU - Majumder, Abdulla Al Shafi

AU - Di Angelantonio, Emanuele

AU - Chowdhury, Rajiv

AU - McCarthy, Mark I.

AU - Poulter, Neil

AU - Stanton, Alice V.

AU - Sever, Peter

AU - Amouyel, Philippe

AU - Arveiler, Dominique

AU - Blankenberg, Stefan

AU - Ferrières, Jean

AU - Kee, Frank

AU - Kuulasmaa, Kari

AU - Müller-Nurasyid, Martina

AU - Veronesi, Giovanni

AU - Virtamo, Jarmo

AU - Deloukas, Panos

AU - Elliott, Paul

AU - Zeggini, Eleftheria

AU - Kathiresan, Sekar

AU - Melander, Olle

AU - Kuusisto, Johanna

AU - Laakso, Markku

AU - Padmanabhan, Sandosh

AU - Porteous, David J.

AU - Hayward, Caroline

AU - Scotland, Generation

AU - Collins, Francis S.

AU - Mohlke, Karen L.

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Boehnke, Michael

AU - Stringham, Heather M.

AU - Frossard, Philippe

AU - Newton-Cheh, Christopher

AU - Tobin, Martin D.

AU - Nordestgaard, Børge Grønne

AU - Caulfield, Mark J.

AU - Mahajan, Anubha

AU - Morris, Andrew P.

AU - Tomaszewski, Maciej

AU - Samani, Nilesh J.

AU - Saleheen, Danish

AU - Asselbergs, Folkert W.

AU - Lindgren, Cecilia M.

AU - Danesh, John

AU - Wain, Louise V.

AU - Butterworth, Adam S.

AU - Howson, Joanna M.M.

AU - Munroe, Patricia B.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - 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 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/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.

AB - 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 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/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.

UR - http://www.scopus.com/inward/record.url?scp=84987670072&partnerID=8YFLogxK

U2 - 10.1038/ng.3654

DO - 10.1038/ng.3654

M3 - Article

C2 - 27618447

AN - SCOPUS:84987670072

VL - 48

SP - 1151

EP - 1161

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 10

ER -

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

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