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 M. Del Greco; 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; 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; 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; Georg B. Ehret

doi:10.1161/HYPERTENSIONAHA.117.09438

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 M. Del Greco, 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, 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, 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, Georg B. Ehret

^*Corresponding author for this work

University of Leicester
Isfahan University of Medical Sciences
VU University Medical Center
Harvard University
National Heart Lung and Blood Institute’s and Boston University’s Framingham Heart Study
Department of Epidemiology
King's College London
Queen Mary University of London
Brigham and Women’s Hospital
Department of Epidemiolagy
Karolinska Institutet
University of Tartu
Boston Children's Hospital
Broad Institute
Johns Hopkins University
National Institutes of Health
Institute for Translational Genomics and Population Sciences
University of Lausanne
Swiss Institute of Bioinformatics
Department of Gerontology and Geriatrics
Institute for Community Medicine
German Centre for Cardiovascular Research
Helmholtz Zentrum München - German Research Center for Environmental Health
Cardiovascular Health Research Unit
Icelandic Heart Association
University of Iceland
Genetic Epidemiology Unit
Fimlab Laboratories
Tampere University
University of Oxford
University of Cambridge
Clinical Division of Neurogeriatrics
Institute of Medical Informatics, Statistics and Documentation
Usher Institute of Population Health Sciences and Informatics
Department of Health
San Raffaele Scientific Institute
Data Tecnica International
Institute of Biomedicine and Translational Medicine
IRCCS Ospedale Infantile Burlo Garofolo - Trieste
University of Trieste
EURAC Research
Department of Genetics and Genomic Sciences
Municipal Institute for Medical Research Hospital del Mar
National Research Council of Italy
University of Edinburgh
Royal College of Surgeons in Ireland
University College Dublin
Uppsala University
University of Michigan, Ann Arbor
University Hospitals of Leicester NHS Trust
School of Public Health
London North West University Healthcare NHS Trust
University of Split
Charles Bronfman Institute for Personalized Medicine
University of Ioannina
University of Dundee
COMSATS University Islamabad
Division of Nephrology
Wellcome Trust Sanger Institute
Institute of Genetics and Molecular Medicine
Centre for Genomic and Experimental Medicine
Department of Clinical Epidemiology
Institut national de la santé et de la recherche médicale
Université de Bordeaux
Hunter Medical Research Institute, Australia
Center for Statistical Genetics
Busselton Population Medical Research Institute
PathWest Laboratory Medicine WA
School of Pathology and Laboratory Medicine
Imperial College Healthcare NHS Trust
Institute of Genetic Medicine
Amsterdam University Medical Centers
Department of Molecular Epidemiology
Stockholm University
Heriot-Watt University
Demography and Biometry
School of Population and Global Health
Imperial College London
Center for Life-Course Health Research
University of Oulu
Cardiovascular Research Center
Center for Human Genetics
University of Geneva
Cardiovascular Epidemiology
Newcastle University
University of Texas Health Science Center at Houston
Interdisciplinary Center Psychopathology and Emotion Regulation (IPCE)
University of Glasgow
University of Helsinki
McMaster University
Department of Psychology
General Central Hospital
University of Lübeck
University of Turku
Fujian Medical University
Department of Biostatistics
University of California at Los Angeles
Medical University of Graz
Etablissement français du sang
University of Newcastle
Hunter New England Health
New York Academy of Medicine
IRCCS Istituto Neurologico Mediterraneo Neuromed - Pozzilli (IS)
University of Glasgow
Department of Genetics
International Centre for Circulatory Health
Commonwealth of Massachusetts
Erasmus University Rotterdam
University of Greifswald
Population Health Research Institute, Ontario
University Hospital of Bordeaux
Leiden University
University of Groningen
Icahn School of Medicine at Mount Sinai
Hammersmith Hospital
National Institute for Health and Welfare
Dasman Diabetes Institute
King Abdulaziz University
University for Continuing Education Krems
University of Manchester
Wake Forest University
University of Washington
Kaiser Permanent Washington Health Research Institute
University of Western Australia
Sir Charles Gairdner Hospital
Department of Cardiology
St. George’s Hospital
Columbia University
Stanford University
Massachusetts General Hospital
Lancaster University
University of Liverpool

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

129 Citations (Scopus)

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.

Original language	English
Pages (from-to)	e4-e19
Journal	Hypertension
Volume	70
Issue number	3
DOIs	https://doi.org/10.1161/HYPERTENSIONAHA.117.09438
Publication status	Published - 1 Sept 2017
Externally published	Yes

Keywords

GWAS
blood pressure
cardiovascular risk
complex traits
eSNP
hypertension

Access to Document

10.1161/HYPERTENSIONAHA.117.09438

Cite this

Wain, L. V., Vaez, A., Jansen, R., Joehanes, R., Van Der Most, P. J., Erzurumluoglu, A. M., O'Reilly, P. F., Cabrera, C. P., Warren, H. R., Rose, L. M., Verwoert, G. C., Hottenga, J. J., Strawbridge, R. J., Esko, T., Arking, D. E., Hwang, S. J., Guo, X., Kutalik, Z., Trompet, S., ... Ehret, G. B. (2017). Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets from Blood and the Kidney. Hypertension, 70(3), e4-e19. https://doi.org/10.1161/HYPERTENSIONAHA.117.09438

@article{5babeb284f034b21b4981c2569857d9c,

title = "Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets from Blood and the Kidney",

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.",

keywords = "GWAS, blood pressure, cardiovascular risk, complex traits, eSNP, hypertension",

author = "Wain, \{Louise V.\} and Ahmad Vaez and Rick Jansen and Roby Joehanes and \{Van Der Most\}, \{Peter J.\} and Erzurumluoglu, \{A. Mesut\} and O'Reilly, \{Paul F.\} and Cabrera, \{Claudia P.\} and Warren, \{Helen R.\} and Rose, \{Lynda M.\} and Verwoert, \{Germaine C.\} and Hottenga, \{Jouke Jan\} and Strawbridge, \{Rona J.\} and Tonu Esko and Arking, \{Dan E.\} and Hwang, \{Shih Jen\} and Xiuqing Guo and Zoltan Kutalik and Stella Trompet and Nick Shrine and Alexander Teumer and Ried, \{Janina S.\} and Bis, \{Joshua C.\} and Smith, \{Albert V.\} and Najaf Amin and Nolte, \{Ilja M.\} and Lyytik{\"a}inen, \{Leo Pekka\} and Anubha Mahajan and Wareham, \{Nicholas J.\} and Edith Hofer and Joshi, \{Peter K.\} and Kati Kristiansson and Michela Traglia and Havulinna, \{Aki S.\} and Anuj Goel and Nalls, \{Mike A.\} and Siim S{\~o}ber and Dragana Vuckovic and Jian'An Luan and \{Del Greco\}, \{Fabiola M.\} and Ayers, \{Kristin L.\} and Jaume Marrugat and Daniela Ruggiero and Lopez, \{Lorna M.\} and Teemu Niiranen and Stefan Enroth and Jackson, \{Anne U.\} and Nelson, \{Christopher P.\} and Huffman, \{Jennifer E.\} and Weihua Zhang and Jonathan Marten and Ilaria Gandin and Harris, \{Sarah E.\} and Tatijana Zemunik and Yingchang Lu and Evangelos Evangelou and Nabi Shah and \{De Borst\}, \{Martin H.\} and Massimo Mangino and Prins, \{Bram P.\} and Archie Campbell and Ruifang Li-Gao and Ganesh Chauhan and Christopher Oldmeadow and Gon{\c c}alo Abecasis and Maryam Abedi and Barbieri, \{Caterina M.\} and Barnes, \{Michael R.\} and Chiara Batini and John Beilby and Tineka Blake and Michael Boehnke and Bottinger, \{Erwin P.\} and Braund, \{Peter S.\} and Morris Brown and Marco Brumat and Harry Campbell and Chambers, \{John C.\} and Massimiliano Cocca and Francis Collins and John Connell and Cordell, \{Heather J.\} and Damman, \{Jeffrey J.\} and Gail Davies and \{De Geus\}, \{Eco J.\} and \{De Mutsert\}, Ren{\'e}e and Joris Deelen and Yusuf Demirkale and Doney, \{Alex S.F.\} and Marcus D{\"o}rr and Martin Farrall and Teresa Ferreira and Mattias Fr{\aa}nberg and He Gao and Vilmantas Giedraitis and Christian Gieger and Franco Giulianini and Gow, \{Alan J.\} and Anders Hamsten and Harris, \{Tamara B.\} and Albert Hofman and Holliday, \{Elizabeth G.\} and Jennie Hui and Jarvelin, \{Marjo Riitta\} and {\AA}sa Johansson and Johnson, \{Andrew D.\} and Pekka Jousilahti and Antti Jula and Mika K{\"a}h{\"o}nen and Sekar Kathiresan and Khaw, \{Kay Tee\} and Ivana Kolcic and Seppo Koskinen and Claudia Langenberg and Marty Larson and Launer, \{Lenore J.\} and Benjamin Lehne and Liewald, \{David C.M.\} and Li Lin and Lars Lind and Fran{\c c}ois Mach and Chrysovalanto Mamasoula and Cristina Menni and Borbala Mifsud and Yuri Milaneschi and Anna Morgan and Morris, \{Andrew D.\} and Morrison, \{Alanna C.\} and Munson, \{Peter J.\} and Priyanka Nandakumar and Nguyen, \{Quang Tri\} and Teresa Nutile and Oldehinkel, \{Albertine J.\} and Oostra, \{Ben A.\} and Elin Org and Sandosh Padmanabhan and Aarno Palotie and Guillaume Par{\'e} and Alison Pattie and Penninx, \{Brenda W.J.H.\} and Neil Poulter and Pramstaller, \{Peter P.\} and Raitakari, \{Olli T.\} and Meixia Ren and Kenneth Rice and Ridker, \{Paul M.\} and Harri{\"e}tte Riese and Samuli Ripatti and Antonietta Robino and Rotter, \{Jerome I.\} and Igor Rudan and Yasaman Saba and \{Saint Pierre\}, Aude and Sala, \{Cinzia F.\} and Sarin, \{Antti Pekka\} and Reinhold Schmidt and Rodney Scott and Seelen, \{Marc A.\} and Shields, \{Denis C.\} and David Siscovick and Rossella Sorice and Alice Stanton and Stott, \{David J.\} and Johan Sundstr{\"o}m and Morris Swertz and Taylor, \{Kent D.\} and Simon Thom and Ioanna Tzoulaki and Christophe Tzourio and Uitterlinden, \{Andr{\'e} G.\} and Uwe V{\"o}lker and Peter Vollenweider and Sarah Wild and Gonneke Willemsen and Wright, \{Alan F.\} and Jie Yao and S{\'e}bastien Th{\'e}riault and David Conen and John Attia and Peter Sever and St{\'e}phanie Debette and Mook-Kanamori, \{Dennis O.\} and Eleftheria Zeggini and Spector, \{Tim D.\} and \{Van Der Harst\}, Pim and Palmer, \{Colin N.A.\} and Vergnaud, \{Anne Claire\} and Loos, \{Ruth J.F.\} and Ozren Polasek and Starr, \{John M.\} and Giorgia Girotto and Caroline Hayward and Kooner, \{Jaspal S.\} and Lindgren, \{Cecila M.\} and Veronique Vitart and Samani, \{Nilesh J.\} and Jaakko Tuomilehto and Ulf Gyllensten and Paul Knekt and Deary, \{Ian J.\} and Marina Ciullo and Roberto Elosua and Keavney, \{Bernard D.\} and Hicks, \{Andrew A.\} and Scott, \{Robert A.\} and Paolo Gasparini and Maris Laan and Yongmei Liu and Hugh Watkins and Hartman, \{Catharina A.\} and Veikko Salomaa and Daniela Toniolo and Markus Perola and Wilson, \{James F.\} and Helena Schmidt and Zhao, \{Jing Hua\} and Terho Lehtim{\"a}ki and \{Van Duijn\}, \{Cornelia M.\} and Vilmundur Gudnason and Psaty, \{Bruce M.\} and Annette Peters and Rainer Rettig and Alan James and Jukema, \{J. Wouter\} and Strachan, \{David P.\} and Walter Palmas and Andres Metspalu and Erik Ingelsson and Boomsma, \{Dorret I.\} and Franco, \{Oscar H.\} and Murielle Bochud and Christopher Newton-Cheh and Munroe, \{Patricia B.\} and Paul Elliott and Chasman, \{Daniel I.\} and Aravinda Chakravarti and Joanne Knight and Morris, \{Andrew P.\} and Daniel Levy and Tobin, \{Martin D.\} and Harold Snieder and Caulfield, \{Mark J.\} and Ehret, \{Georg B.\}",

note = "Publisher Copyright: {\textcopyright} 2017 American Heart Association, Inc.",

year = "2017",

month = sep,

day = "1",

doi = "10.1161/HYPERTENSIONAHA.117.09438",

language = "English",

volume = "70",

pages = "e4--e19",

journal = "Hypertension",

issn = "0194-911X",

publisher = "Lippincott Williams and Wilkins",

number = "3",

}

Wain, LV, Vaez, A, Jansen, R, Joehanes, R, Van Der Most, PJ, Erzurumluoglu, AM, O'Reilly, PF, Cabrera, CP, Warren, HR, Rose, LM, Verwoert, GC, Hottenga, JJ, Strawbridge, RJ, Esko, T, Arking, DE, Hwang, SJ, Guo, X, Kutalik, Z, Trompet, S, Shrine, N, Teumer, A, Ried, JS, Bis, JC, Smith, AV, Amin, N, Nolte, IM, Lyytikäinen, LP, Mahajan, A, Wareham, NJ, Hofer, E, Joshi, PK, Kristiansson, K, Traglia, M, Havulinna, AS, Goel, A, Nalls, MA, Sõber, S, Vuckovic, D, Luan, JA, Del Greco, FM, Ayers, KL, Marrugat, J, Ruggiero, D, Lopez, LM, Niiranen, T, Enroth, S, Jackson, AU, Nelson, CP, Huffman, JE, Zhang, W, Marten, J, Gandin, I, Harris, SE, Zemunik, T, Lu, Y, Evangelou, E, Shah, N, De Borst, MH, Mangino, M, Prins, BP, Campbell, A, Li-Gao, R, Chauhan, G, Oldmeadow, C, Abecasis, G, Abedi, M, Barbieri, CM, Barnes, MR, Batini, C, Beilby, J, Blake, T, Boehnke, M, Bottinger, EP, Braund, PS, Brown, M, Brumat, M, Campbell, H, Chambers, JC, Cocca, M, Collins, F, Connell, J, Cordell, HJ, Damman, JJ, Davies, G, De Geus, EJ, De Mutsert, R, Deelen, J, Demirkale, Y, Doney, ASF, Dörr, M, Farrall, M, Ferreira, T, Frånberg, M, Gao, H, Giedraitis, V, Gieger, C, Giulianini, F, Gow, AJ, Hamsten, A, Harris, TB, Hofman, A, Holliday, EG, Hui, J, Jarvelin, MR, Johansson, Å, Johnson, AD, Jousilahti, P, Jula, A, Kähönen, M, Kathiresan, S, Khaw, KT, Kolcic, I, Koskinen, S, Langenberg, C, Larson, M, Launer, LJ, Lehne, B, Liewald, DCM, Lin, L, Lind, L, Mach, F, Mamasoula, C, Menni, C, Mifsud, B, Milaneschi, Y, Morgan, A, Morris, AD, Morrison, AC, Munson, PJ, Nandakumar, P, Nguyen, QT, Nutile, T, Oldehinkel, AJ, Oostra, BA, Org, E, Padmanabhan, S, Palotie, A, Paré, G, Pattie, A, Penninx, BWJH, Poulter, N, Pramstaller, PP, Raitakari, OT, Ren, M, Rice, K, Ridker, PM, Riese, H, Ripatti, S, Robino, A, Rotter, JI, Rudan, I, Saba, Y, Saint Pierre, A, Sala, CF, Sarin, AP, Schmidt, R, Scott, R, Seelen, MA, Shields, DC, Siscovick, D, Sorice, R, Stanton, A, Stott, DJ, Sundström, J, Swertz, M, Taylor, KD, Thom, S, Tzoulaki, I, Tzourio, C, Uitterlinden, AG, Völker, U, Vollenweider, P, Wild, S, Willemsen, G, Wright, AF, Yao, J, Thériault, S, Conen, D, Attia, J, Sever, P, Debette, S, Mook-Kanamori, DO, Zeggini, E, Spector, TD, Van Der Harst, P, Palmer, CNA, Vergnaud, AC, Loos, RJF, Polasek, O, Starr, JM, Girotto, G, Hayward, C, Kooner, JS, Lindgren, CM, Vitart, V, Samani, NJ, Tuomilehto, J, Gyllensten, U, Knekt, P, Deary, IJ, Ciullo, M, Elosua, R, Keavney, BD, Hicks, AA, Scott, RA, Gasparini, P, Laan, M, Liu, Y, Watkins, H, Hartman, CA, Salomaa, V, Toniolo, D, Perola, M, Wilson, JF, Schmidt, H, Zhao, JH, Lehtimäki, T, Van Duijn, CM, Gudnason, V, Psaty, BM, Peters, A, Rettig, R, James, A, Jukema, JW, Strachan, DP, Palmas, W, Metspalu, A, Ingelsson, E, Boomsma, DI, Franco, OH, Bochud, M, Newton-Cheh, C, Munroe, PB, Elliott, P, Chasman, DI, Chakravarti, A, Knight, J, Morris, AP, Levy, D, Tobin, MD, Snieder, H, Caulfield, MJ & Ehret, GB 2017, 'Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets from Blood and the Kidney', Hypertension, vol. 70, no. 3, pp. e4-e19. https://doi.org/10.1161/HYPERTENSIONAHA.117.09438

TY - JOUR

T1 - Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets from Blood and the Kidney

AU - Wain, Louise V.

AU - Vaez, Ahmad

AU - Jansen, Rick

AU - Joehanes, Roby

AU - Van Der Most, Peter J.

AU - Erzurumluoglu, A. Mesut

AU - O'Reilly, Paul F.

AU - Cabrera, Claudia P.

AU - Warren, Helen R.

AU - Rose, Lynda M.

AU - Verwoert, Germaine C.

AU - Hottenga, Jouke Jan

AU - Strawbridge, Rona J.

AU - Esko, Tonu

AU - Arking, Dan E.

AU - Hwang, Shih Jen

AU - Guo, Xiuqing

AU - Kutalik, Zoltan

AU - Trompet, Stella

AU - Shrine, Nick

AU - Teumer, Alexander

AU - Ried, Janina S.

AU - Bis, Joshua C.

AU - Smith, Albert V.

AU - Amin, Najaf

AU - Nolte, Ilja M.

AU - Lyytikäinen, Leo Pekka

AU - Mahajan, Anubha

AU - Wareham, Nicholas J.

AU - Hofer, Edith

AU - Joshi, Peter K.

AU - Kristiansson, Kati

AU - Traglia, Michela

AU - Havulinna, Aki S.

AU - Goel, Anuj

AU - Nalls, Mike A.

AU - Sõber, Siim

AU - Vuckovic, Dragana

AU - Luan, Jian'An

AU - Del Greco, Fabiola M.

AU - Ayers, Kristin L.

AU - Marrugat, Jaume

AU - Ruggiero, Daniela

AU - Lopez, Lorna M.

AU - Niiranen, Teemu

AU - Enroth, Stefan

AU - Jackson, Anne U.

AU - Nelson, Christopher P.

AU - Huffman, Jennifer E.

AU - Zhang, Weihua

AU - Marten, Jonathan

AU - Gandin, Ilaria

AU - Harris, Sarah E.

AU - Zemunik, Tatijana

AU - Lu, Yingchang

AU - Evangelou, Evangelos

AU - Shah, Nabi

AU - De Borst, Martin H.

AU - Mangino, Massimo

AU - Prins, Bram P.

AU - Campbell, Archie

AU - Li-Gao, Ruifang

AU - Chauhan, Ganesh

AU - Oldmeadow, Christopher

AU - Abecasis, Gonçalo

AU - Abedi, Maryam

AU - Barbieri, Caterina M.

AU - Barnes, Michael R.

AU - Batini, Chiara

AU - Beilby, John

AU - Blake, Tineka

AU - Boehnke, Michael

AU - Bottinger, Erwin P.

AU - Braund, Peter S.

AU - Brown, Morris

AU - Brumat, Marco

AU - Campbell, Harry

AU - Chambers, John C.

AU - Cocca, Massimiliano

AU - Collins, Francis

AU - Connell, John

AU - Cordell, Heather J.

AU - Damman, Jeffrey J.

AU - Davies, Gail

AU - De Geus, Eco J.

AU - De Mutsert, Renée

AU - Deelen, Joris

AU - Demirkale, Yusuf

AU - Doney, Alex S.F.

AU - Dörr, Marcus

AU - Farrall, Martin

AU - Ferreira, Teresa

AU - Frånberg, Mattias

AU - Gao, He

AU - Giedraitis, Vilmantas

AU - Gieger, Christian

AU - Giulianini, Franco

AU - Gow, Alan J.

AU - Hamsten, Anders

AU - Harris, Tamara B.

AU - Hofman, Albert

AU - Holliday, Elizabeth G.

AU - Hui, Jennie

AU - Jarvelin, Marjo Riitta

AU - Johansson, Åsa

AU - Johnson, Andrew D.

AU - Jousilahti, Pekka

AU - Jula, Antti

AU - Kähönen, Mika

AU - Kathiresan, Sekar

AU - Khaw, Kay Tee

AU - Kolcic, Ivana

AU - Koskinen, Seppo

AU - Langenberg, Claudia

AU - Larson, Marty

AU - Launer, Lenore J.

AU - Lehne, Benjamin

AU - Liewald, David C.M.

AU - Lin, Li

AU - Lind, Lars

AU - Mach, François

AU - Mamasoula, Chrysovalanto

AU - Menni, Cristina

AU - Mifsud, Borbala

AU - Milaneschi, Yuri

AU - Morgan, Anna

AU - Morris, Andrew D.

AU - Morrison, Alanna C.

AU - Munson, Peter J.

AU - Nandakumar, Priyanka

AU - Nguyen, Quang Tri

AU - Nutile, Teresa

AU - Oldehinkel, Albertine J.

AU - Oostra, Ben A.

AU - Org, Elin

AU - Padmanabhan, Sandosh

AU - Palotie, Aarno

AU - Paré, Guillaume

AU - Pattie, Alison

AU - Penninx, Brenda W.J.H.

AU - Poulter, Neil

AU - Pramstaller, Peter P.

AU - Raitakari, Olli T.

AU - Ren, Meixia

AU - Rice, Kenneth

AU - Ridker, Paul M.

AU - Riese, Harriëtte

AU - Ripatti, Samuli

AU - Robino, Antonietta

AU - Rotter, Jerome I.

AU - Rudan, Igor

AU - Saba, Yasaman

AU - Saint Pierre, Aude

AU - Sala, Cinzia F.

AU - Sarin, Antti Pekka

AU - Schmidt, Reinhold

AU - Scott, Rodney

AU - Seelen, Marc A.

AU - Shields, Denis C.

AU - Siscovick, David

AU - Sorice, Rossella

AU - Stanton, Alice

AU - Stott, David J.

AU - Sundström, Johan

AU - Swertz, Morris

AU - Taylor, Kent D.

AU - Thom, Simon

AU - Tzoulaki, Ioanna

AU - Tzourio, Christophe

AU - Uitterlinden, André G.

AU - Völker, Uwe

AU - Vollenweider, Peter

AU - Wild, Sarah

AU - Willemsen, Gonneke

AU - Wright, Alan F.

AU - Yao, Jie

AU - Thériault, Sébastien

AU - Conen, David

AU - Attia, John

AU - Sever, Peter

AU - Debette, Stéphanie

AU - Mook-Kanamori, Dennis O.

AU - Zeggini, Eleftheria

AU - Spector, Tim D.

AU - Van Der Harst, Pim

AU - Palmer, Colin N.A.

AU - Vergnaud, Anne Claire

AU - Loos, Ruth J.F.

AU - Polasek, Ozren

AU - Starr, John M.

AU - Girotto, Giorgia

AU - Hayward, Caroline

AU - Kooner, Jaspal S.

AU - Lindgren, Cecila M.

AU - Vitart, Veronique

AU - Samani, Nilesh J.

AU - Tuomilehto, Jaakko

AU - Gyllensten, Ulf

AU - Knekt, Paul

AU - Deary, Ian J.

AU - Ciullo, Marina

AU - Elosua, Roberto

AU - Keavney, Bernard D.

AU - Hicks, Andrew A.

AU - Scott, Robert A.

AU - Gasparini, Paolo

AU - Laan, Maris

AU - Liu, Yongmei

AU - Watkins, Hugh

AU - Hartman, Catharina A.

AU - Salomaa, Veikko

AU - Toniolo, Daniela

AU - Perola, Markus

AU - Wilson, James F.

AU - Schmidt, Helena

AU - Zhao, Jing Hua

AU - Lehtimäki, Terho

AU - Van Duijn, Cornelia M.

AU - Gudnason, Vilmundur

AU - Psaty, Bruce M.

AU - Peters, Annette

AU - Rettig, Rainer

AU - James, Alan

AU - Jukema, J. Wouter

AU - Strachan, David P.

AU - Palmas, Walter

AU - Metspalu, Andres

AU - Ingelsson, Erik

AU - Boomsma, Dorret I.

AU - Franco, Oscar H.

AU - Bochud, Murielle

AU - Newton-Cheh, Christopher

AU - Munroe, Patricia B.

AU - Elliott, Paul

AU - Chasman, Daniel I.

AU - Chakravarti, Aravinda

AU - Knight, Joanne

AU - Morris, Andrew P.

AU - Levy, Daniel

AU - Tobin, Martin D.

AU - Snieder, Harold

AU - Caulfield, Mark J.

AU - Ehret, Georg B.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

AB - 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.

KW - GWAS

KW - blood pressure

KW - cardiovascular risk

KW - complex traits

KW - eSNP

KW - hypertension

UR - https://www.scopus.com/pages/publications/85027077950

U2 - 10.1161/HYPERTENSIONAHA.117.09438

DO - 10.1161/HYPERTENSIONAHA.117.09438

M3 - Article

C2 - 28739976

AN - SCOPUS:85027077950

SN - 0194-911X

VL - 70

SP - e4-e19

JO - Hypertension

JF - Hypertension

IS - 3

ER -

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets from Blood and the Kidney

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