Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
File(s)HYPE201709438.pdf (291.05 KB)
Accepted version
Author(s)
Poulter, NR
et al
Type
Journal Article
Abstract
Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project–based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
Date Issued
2017-07-24
Date Acceptance
2017-07-12
Citation
Hypertension, 2017, 70, pp.e4-e19
ISSN
0194-911X
Publisher
Wolters Kluwer Health
Start Page
e4
End Page
e19
Journal / Book Title
Hypertension
Volume
70
Copyright Statement
© 2017 Lippincott Williams & Wilkins, Inc. This is a non-final version of an article published in final form in Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
Louise V. Wain, Ahmad Vaez, Rick Jansen, Roby Joehanes, Peter J. van der Most, A. Mesut Erzurumluoglu, Paul F. O’Reilly, Claudia P. Cabrera, Helen R. Warren, Lynda M. Rose, Germaine C. Verwoert, Jouke-Jan Hottenga, Rona J. Strawbridge, Tonu Esko, Dan E. Arking, Shih-Jen Hwang, Xiuqing Guo, Zoltan Kutalik, Stella Trompet, Nick Shrine, Alexander Teumer, Janina S. Ried, Joshua C. Bis, Albert V. Smith, Najaf Amin, Ilja M. Nolte, Leo-Pekka Lyytikäinen, Anubha Mahajan, Nicholas J. Wareham, Edith Hofer, Peter K. Joshi, Kati Kristiansson, Michela Traglia, Aki S. Havulinna, Anuj Goel, Mike A. Nalls, Siim Sõber, Dragana Vuckovic, Jian’an Luan, Fabiola Del Greco M., Kristin L. Ayers, Jaume Marrugat, Daniela Ruggiero, Lorna M. Lopez, Teemu Niiranen, Stefan Enroth, Anne U. Jackson, Christopher P. Nelson, Jennifer E. Huffman, Weihua Zhang, Jonathan Marten, Ilaria Gandin, Sarah E. Harris, Tatijana Zemunik, Yingchang Lu, Evangelos Evangelou, Nabi Shah, Martin H. de Borst, Massimo Mangino, Bram P. Prins, Archie Campbell, Ruifang Li-Gao, Ganesh Chauhan, Christopher Oldmeadow, Gonçalo Abecasis, Maryam Abedi, Caterina M. Barbieri, Michael R. Barnes, Chiara Batini, John Beilby, BIOS Consortium, Tineka Blake, Michael Boehnke, Erwin P. Bottinger, Peter S. Braund, Morris Brown, Marco Brumat, Harry Campbell, John C. Chambers, Massimiliano Cocca, Francis Collins, John Connell, Heather J. Cordell, Jeffrey J. Damman, Gail Davies, Eco J. de Geus, Renée de Mutsert, Joris Deelen, Yusuf Demirkale, Alex S.F. Doney, Marcus Dörr, Martin Farrall, Teresa Ferreira, Mattias Frånberg, He Gao, Vilmantas Giedraitis, Christian Gieger, Franco Giulianini, Alan J. Gow, Anders Hamsten, Tamara B. Harris, Albert Hofman, Elizabeth G. Holliday, Jennie Hui, Marjo-Riitta Jarvelin, Åsa Johansson, Andrew D. Johnson, Pekka Jousilahti, Antti Jula, Mika Kähönen, Sekar Kathiresan, Kay-Tee Khaw, Ivana Kolcic, Seppo Koskinen, Claudia Langenberg, Marty Larson, Lenore J. Launer, Benjamin Lehne, David C.M. Liewald, Li Lin, Lars Lind, François Mach, Chrysovalanto Mamasoula, Cristina Menni, Borbala Mifsud, Yuri Milaneschi, Anna Morgan, Andrew D. Morris, Alanna C. Morrison, Peter J. Munson, Priyanka Nandakumar, Quang Tri Nguyen, Teresa Nutile, Albertine J. Oldehinkel, Ben A. Oostra, Elin Org, Sandosh Padmanabhan, Aarno Palotie, Guillaume Paré, Alison Pattie, Brenda W.J.H. Penninx, Neil Poulter, Peter P. Pramstaller, Olli T. Raitakari, Meixia Ren, Kenneth Rice, Paul M. Ridker, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Jerome I. Rotter, Igor Rudan, Yasaman Saba, Aude Saint Pierre, Cinzia F. Sala, Antti-Pekka Sarin, Reinhold Schmidt, Rodney Scott, Marc A. Seelen, Denis C. Shields, David Siscovick, Rossella Sorice, Alice Stanton, David J. Stott, Johan Sundström, Morris Swertz, Kent D. Taylor, Simon Thom, Ioanna Tzoulaki, Christophe Tzourio, André G. Uitterlinden, Understanding Society Scientific Group, Uwe Völker, Peter Vollenweider, Sarah Wild, Gonneke Willemsen, Alan F. Wright, Jie Yao, Sébastien Thériault, David Conen, John Attia, Peter Sever, Stéphanie Debette, Dennis O. Mook-Kanamori, Eleftheria Zeggini, Tim D. Spector, Pim van der Harst, Colin N.A. Palmer, Anne-Claire Vergnaud, Ruth J.F. Loos, Ozren Polasek, John M. Starr, Giorgia Girotto, Caroline Hayward, Jaspal S. Kooner, Cecila M. Lindgren, Veronique Vitart, Nilesh J. Samani, Jaakko Tuomilehto, Ulf Gyllensten, Paul Knekt, Ian J. Deary, Marina Ciullo, Roberto Elosua, Bernard D. Keavney, Andrew A. Hicks, Robert A. Scott, Paolo Gasparini, Maris Laan, YongMei Liu, Hugh Watkins, Catharina A. Hartman, Veikko Salomaa, Daniela Toniolo, Markus Perola, James F. Wilson, Helena Schmidt, Jing Hua Zhao, Terho Lehtimäki, Cornelia M. van Duijn, Vilmundur Gudnason, Bruce M. Psaty, Annette Peters, Rainer Rettig, Alan James, J. Wouter Jukema, David P. Strachan, Walter Palmas, Andres Metspalu, Erik Ingelsson, Dorret I. Boomsma, Oscar H. Franco, Murielle Bochud, Christopher Newton-Cheh, Patricia B. Munroe, Paul Elliott, Daniel I. Chasman, Aravinda Chakravarti, Joanne Knight, Andrew P. Morris, Daniel Levy, Martin D. Tobin, Harold Snieder, Mark J. Caulfield and Georg B. Ehret
Hypertension. 2017;70:e4-e19, originally published July 24, 2017. https://dx.doi.org/10.1161/HYPERTENSIONAHA.117.09438
Louise V. Wain, Ahmad Vaez, Rick Jansen, Roby Joehanes, Peter J. van der Most, A. Mesut Erzurumluoglu, Paul F. O’Reilly, Claudia P. Cabrera, Helen R. Warren, Lynda M. Rose, Germaine C. Verwoert, Jouke-Jan Hottenga, Rona J. Strawbridge, Tonu Esko, Dan E. Arking, Shih-Jen Hwang, Xiuqing Guo, Zoltan Kutalik, Stella Trompet, Nick Shrine, Alexander Teumer, Janina S. Ried, Joshua C. Bis, Albert V. Smith, Najaf Amin, Ilja M. Nolte, Leo-Pekka Lyytikäinen, Anubha Mahajan, Nicholas J. Wareham, Edith Hofer, Peter K. Joshi, Kati Kristiansson, Michela Traglia, Aki S. Havulinna, Anuj Goel, Mike A. Nalls, Siim Sõber, Dragana Vuckovic, Jian’an Luan, Fabiola Del Greco M., Kristin L. Ayers, Jaume Marrugat, Daniela Ruggiero, Lorna M. Lopez, Teemu Niiranen, Stefan Enroth, Anne U. Jackson, Christopher P. Nelson, Jennifer E. Huffman, Weihua Zhang, Jonathan Marten, Ilaria Gandin, Sarah E. Harris, Tatijana Zemunik, Yingchang Lu, Evangelos Evangelou, Nabi Shah, Martin H. de Borst, Massimo Mangino, Bram P. Prins, Archie Campbell, Ruifang Li-Gao, Ganesh Chauhan, Christopher Oldmeadow, Gonçalo Abecasis, Maryam Abedi, Caterina M. Barbieri, Michael R. Barnes, Chiara Batini, John Beilby, BIOS Consortium, Tineka Blake, Michael Boehnke, Erwin P. Bottinger, Peter S. Braund, Morris Brown, Marco Brumat, Harry Campbell, John C. Chambers, Massimiliano Cocca, Francis Collins, John Connell, Heather J. Cordell, Jeffrey J. Damman, Gail Davies, Eco J. de Geus, Renée de Mutsert, Joris Deelen, Yusuf Demirkale, Alex S.F. Doney, Marcus Dörr, Martin Farrall, Teresa Ferreira, Mattias Frånberg, He Gao, Vilmantas Giedraitis, Christian Gieger, Franco Giulianini, Alan J. Gow, Anders Hamsten, Tamara B. Harris, Albert Hofman, Elizabeth G. Holliday, Jennie Hui, Marjo-Riitta Jarvelin, Åsa Johansson, Andrew D. Johnson, Pekka Jousilahti, Antti Jula, Mika Kähönen, Sekar Kathiresan, Kay-Tee Khaw, Ivana Kolcic, Seppo Koskinen, Claudia Langenberg, Marty Larson, Lenore J. Launer, Benjamin Lehne, David C.M. Liewald, Li Lin, Lars Lind, François Mach, Chrysovalanto Mamasoula, Cristina Menni, Borbala Mifsud, Yuri Milaneschi, Anna Morgan, Andrew D. Morris, Alanna C. Morrison, Peter J. Munson, Priyanka Nandakumar, Quang Tri Nguyen, Teresa Nutile, Albertine J. Oldehinkel, Ben A. Oostra, Elin Org, Sandosh Padmanabhan, Aarno Palotie, Guillaume Paré, Alison Pattie, Brenda W.J.H. Penninx, Neil Poulter, Peter P. Pramstaller, Olli T. Raitakari, Meixia Ren, Kenneth Rice, Paul M. Ridker, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Jerome I. Rotter, Igor Rudan, Yasaman Saba, Aude Saint Pierre, Cinzia F. Sala, Antti-Pekka Sarin, Reinhold Schmidt, Rodney Scott, Marc A. Seelen, Denis C. Shields, David Siscovick, Rossella Sorice, Alice Stanton, David J. Stott, Johan Sundström, Morris Swertz, Kent D. Taylor, Simon Thom, Ioanna Tzoulaki, Christophe Tzourio, André G. Uitterlinden, Understanding Society Scientific Group, Uwe Völker, Peter Vollenweider, Sarah Wild, Gonneke Willemsen, Alan F. Wright, Jie Yao, Sébastien Thériault, David Conen, John Attia, Peter Sever, Stéphanie Debette, Dennis O. Mook-Kanamori, Eleftheria Zeggini, Tim D. Spector, Pim van der Harst, Colin N.A. Palmer, Anne-Claire Vergnaud, Ruth J.F. Loos, Ozren Polasek, John M. Starr, Giorgia Girotto, Caroline Hayward, Jaspal S. Kooner, Cecila M. Lindgren, Veronique Vitart, Nilesh J. Samani, Jaakko Tuomilehto, Ulf Gyllensten, Paul Knekt, Ian J. Deary, Marina Ciullo, Roberto Elosua, Bernard D. Keavney, Andrew A. Hicks, Robert A. Scott, Paolo Gasparini, Maris Laan, YongMei Liu, Hugh Watkins, Catharina A. Hartman, Veikko Salomaa, Daniela Toniolo, Markus Perola, James F. Wilson, Helena Schmidt, Jing Hua Zhao, Terho Lehtimäki, Cornelia M. van Duijn, Vilmundur Gudnason, Bruce M. Psaty, Annette Peters, Rainer Rettig, Alan James, J. Wouter Jukema, David P. Strachan, Walter Palmas, Andres Metspalu, Erik Ingelsson, Dorret I. Boomsma, Oscar H. Franco, Murielle Bochud, Christopher Newton-Cheh, Patricia B. Munroe, Paul Elliott, Daniel I. Chasman, Aravinda Chakravarti, Joanne Knight, Andrew P. Morris, Daniel Levy, Martin D. Tobin, Harold Snieder, Mark J. Caulfield and Georg B. Ehret
Hypertension. 2017;70:e4-e19, originally published July 24, 2017. https://dx.doi.org/10.1161/HYPERTENSIONAHA.117.09438
Sponsor
Home Office
Medical Research Council (MRC)
Medical Research Council (MRC)
National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
British Heart Foundation
Medical Research Council (MRC)
Medical Research Council (MRC)
National Institute for Health Research
Grant Number
PG0484
G0700931
G0601966
NF-SI-0611-10136
RDC01 79560
SP/13/2/30111
MR/L01632X/1
MR/L01341X/1
RTJ6219303-1
Subjects
GWAS
blood pressure
cardiovascular risk
complex traits
eSNP
hypertension
1103 Clinical Sciences
1102 Cardiovascular Medicine And Haematology
Cardiovascular System & Hematology
Publication Status
Published