Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

• Main Authors: Warren, Helen R, Evangelou, Evangelos, Cabrera, Claudia P, Gao, He, Ren, Meixia, Mifsud, Borbala, Ntalla, Ioanna, Surendran, Praveen, Liu, Chunyu, Cook, James P, Kraja, Aldi T, Drenos, Fotios, Loh, Marie, Verweij, Niek, Marten, Jonathan, Karaman, Ibrahim, Lepe, Marcelo P Segura, O'Reilly, Paul F, Knight, Joanne, Snieder, Harold, Kato, Norihiro, He, Jiang, Tai, E Shyong, Said, M Abdullah, Porteous, David, Alver, Maris, Poulter, Neil, Farrall, Martin, Gansevoort, Ron T, Padmanabhan, Sandosh, Mägi, Reedik, Stanton, Alice, Connell, John, Bakker, Stephan J L, Metspalu, Andres, Shields, Denis C, Thom, Simon, Brown, Morris, Sever, Peter, Esko, Tõnu, Hayward, Caroline, van der Harst, Pim, Saleheen, Danish, Chowdhury, Rajiv, Chasman, Daniel I, Chakravarti, Aravinda, Newton-Cheh, Christopher, Lindgren, Cecilia M, Levy, Daniel, Kooner, Jaspal S, Keavney, Bernard, Tomaszewski, Maciej, Samani, Nilesh J, Howson, Joanna M M, Tobin, Martin D, Munroe, Patricia B, Ehret, Georg B, Wain, Louise V, Vaez, Ahmad, Jansen, Rick, Joehanes, Roby, van der Most, Peter J, Erzurumluoglu, A Mesut, O'Reilly, Paul, Rose, Lynda M, Verwoert, Germaine C, Hottenga, Jouke-Jan, Strawbridge, Rona J, Esko, Tonu, Arking, Dan E, Hwang, Shih-Jen, Guo, Xiuqing, Kutalik, Zoltan, Trompet, Stella, Shrine, Nick, Teumer, Alexander, Ried, Janina S, Bis, Joshua C, Smith, Albert V, Amin, Najaf, Nolte, Ilja M, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Wareham, Nicholas J, Hofer, Edith, Joshi, Peter K, Kristiansson, Kati, Traglia, Michela, Havulinna, Aki S, Goel, Anuj, Nalls, Mike A, Sõber, Siim, Vuckovic, Dragana, Luan, Jian'an, M, Fabiola Del Greco, Ayers, Kristin L, Marrugat, Jaume, Ruggiero, Daniela, Lopez, Lorna M, Niiranen, Teemu, Enroth, Stefan, Jackson, Anne U, Nelson, Christopher P, Huffman, Jennifer E, Zhang, Weihua, Gandin, Ilaria, Harris, Sarah E, Zemonik, Tatijana, Lu, Yingchang, Shah, Nabi, de Borst, Martin H, Mangino, Massimo, Prins, Bram P, Campbell, Archie, Li-Gao, Ruifang, Chauhan, Ganesh, Oldmeadow, Christopher, Abecasis, Gonçalo, Abedi, Maryam, Barbieri, Caterina M, Barnes, Michael R, Batini, Chiara, Blake, Tineka, Boehnke, Michael, Bottinger, Erwin P, Braund, Peter S, Brumat, Marco, Campbell, Harry, Chambers, John Campbell, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J, Damman, Jeffrey J, Davies, Gail, de Geus, Eco J, de Mutsert, Renée, Deelen, Joris, Demirkale, Yusuf, Doney, Alex S F, Dörr, Marcus, Ferreira, Teresa, Frånberg, Mattias, Giedraitis, Vilmantas, Gieger, Christian, Giulianini, Franco, Gow, Alan J, Hamsten, Anders, Harris, Tamara B, Hofman, Albert, Holliday, Elizabeth G, Jarvelin, Marjo-Riitta, Johansson, Åsa, Johnson, Andrew D, Jousilahti, Pekka, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Khaw, Kay-Tee, Kolcic, Ivana, Koskinen, Seppo, Langenberg, Claudia, Larson, Marty, Launer, Lenore J, Lehne, Benjamin, Liewald, David C M, Lin, Li, Lind, Lars, Mach, François, Mamasoula, Chrysovalanto, Menni, Cristina, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew D, Morrison, Alanna C, Munson, Peter J, Nandakumar, Priyanka, Nguyen, Quang Tri, Nutile, Teresa, Oldehinkel, Albertine J, Oostra, Ben A, Org, Elin, Palotie, Aarno, Paré, Guillaume, Pattie, Alison, Penninx, Brenda W J H, Pramstaller, Peter P, Raitakari, Olli T, Rice, Kenneth, Ridker, Paul M, Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rotter, Jerome I, Rudan, Igor, Saba, Yasaman, Pierre, Aude Saint, Sala, Cinzia F, Sarin, Antti-Pekka, Schmidt, Reinhold, Scott, Rodney, Seelen, Marc A, Siscovick, David, Sorice, Rossella, Stott, David J, Sundström, Johan, Swertz, Morris, Taylor, Kent D, Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, André G, Völker, Uwe, Vollenweider, Peter, Wild, Sarah, Willemsen, Gonneke, Hartman, Catharina A, Wright, Alan F, Yao, Jie, Thériault, Sébastien, Conen, David, John, Attia, Debette, Stéphanie, Mook-Kanamori, Dennis O, Zeggini, Eleftheria, Spector, Tim D, Palmer, Colin N A, Vergnaud, Anne-Claire, Loos, Ruth J F, Polasek, Ozren, Starr, John M, Girotto, Giorgia, Lindgren, Cecila M, Vitart, Veronique, Tuomilehto, Jaakko, Watkins, Hugh, Gyllensten, Ulf, Knekt, Paul, Deary, Ian J, Ciullo, Marina, Elosua, Roberto, Keavney, Bernard D, Hicks, Andrew A, Scott, Robert A, Gasparini, Paolo, Laan, Maris, Liu, YongMei, Salomaa, Veikko, Toniolo, Daniela, Perola, Markus, Wilson, James F, Schmidt, Helena, Zhao, Jing Hua, Lehtimäki, Terho, van Duijn, Cornelia M, Gudnason, Vilmundur, Psaty, Bruce M, Peters, Annette, Rettig, Rainer, James, Alan, Jukema, J Wouter, Strachan, David P, Palmas, Walter, Ingelsson, Erik, Boomsma, Dorret I, Franco, Oscar H, Bochud, Murielle, Elliott, Paul, Morris, Andrew P, Caulfield, Mark J
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2017
• Subjects: Cardiovascular Risk; Blood Pressure
• Online Access: https://hdl.handle.net/10356/83864; http://hdl.handle.net/10220/42921
• Institution: Nanyang Technological University

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early