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Novel blood pressure locus and gene discovery using GWAS and expression datasets from blood and the kidney

By Louise V Wain, Ahmad Vaez, Rick Jansen, Roby Joehanes, Peter J van der Most, A Mesut Erzurumluoglu, Paul 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 Zemonik, 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 CM Liewald, Lifelines Cohort Study, 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 Vöker, Peter Vollenweider, Sarah Wild, Gonneke Willemsen, Alan F. Wright, Jie Yao, Sébastien Thériault, David Conen, Attia John, 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 JF 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

Posted 22 Feb 2017
bioRxiv DOI: 10.1101/110833 (published DOI: 10.1161/HYPERTENSIONAHA.117.09438)

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 BP 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.

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