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 ShrineAlexander Teumer, Janina S. Ried, Joshua C. Bis, Albert V. Smith, Najaf Amin, Ilja M. Nolte, Leo-Pekka Lyytikainen, Anubha Mahajan, Nicholas J. Wareham, Edith Hofer, Peter K. Joshi, Kati Kristiansson, Michela Traglia, Aki S. Havulinna, Anuj Goel, Mike A. Nalls, Siim Sober, 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, Goncalo 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, Renee de Mutsert, Joris Deelen, Yusuf Demirkale, Alex S. F. Doney, Marcus Dorr, Martin Farrall, Teresa Ferreira, Mattias Franberg, 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, Asa Johansson, Andrew D. Johnson, Pekka Jousilahti, Antti Jula, Mika Kahonen, 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, Francois 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 Pare, Alison Pattie, Brenda W. J. H. Penninx, Neil Poulter, Peter P. Pramstaller, Olli T. Raitakari, Meixia Ren, Kenneth Rice, Paul M. Ridker, Harriette 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 Sundstrom, Morris Swertz, Kent D. Taylor, Simon Thom, Ioanna Tzoulaki, Christophe Tzourio, Andre G. Uitterlinden, Uwe Volker, Peter Vollenweider, Sarah Wild, Gonneke Willemsen, Alan F. Wright, Jie Yao, Sebastien Theriault, David Conen, John Attia, Peter Sever, Stephanie 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, et al.

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

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 languageAmerican English
Pages (from-to)E4-+
JournalHYPERTENSION
Volume70
Issue number3
DOIs
StatePublished - 2017
Externally publishedYes

Funding Agency

  • Kuwait Foundation for the Advancement of Sciences

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