1. Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk
- Author
-
Warren, Helen R., Evangelou, Evangelos, Cabrera, Claudia P., Gao, 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, Jiang, Tai, E. Shyong, Said, M. Abdullah, Porteous, David, Alver, Maris, Poulter, Neil, Farrall, Martin, Gansevoort, Ron T., Padmanabhan, Sandosh, Magi, Reedik, Stanton, Alice, Connell, John, Bakker, Stephan J. L., Metspalu, Andres, Shields, Denis C., Thom, Simon, Brown, Morris, Sever, Peter, Esko, Tonu, Hayward, Caroline, van der Harst, Pim, Saleheen, Danish, Chowdhury, Rajiv, Chambers, John C., 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., Barnes, Michael R., Tzoulaki, Joanna, Caulfield, Mark J., Elliott, Paul, Vaez, Ahmad, Jansen, Rick, Joehanes, Roby, van der Most, Peter J., Erzurumluoglu, A. Mesut, Rose, Lynda M., Verwoert, Germaine C., Hottenga, Jouke-Jan, Strawbridge, Rona J., 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., Lyytikainen, Leo-Pekka, Mahajan, Anubha, Wareham, Nicholas J., Hofer, Edith, Joshi, Peter K., Kristiansson, Kati, Traglia, Michela, Havulinna, Aki S., Goel, Anuj, Nalls, Mike A., Sober, Siim, Vuckovic, Dragana, Luan, Jian'an, Del Greco M, Fabiola, 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, Yingchang, Shah, Nabi, de Borst, Martin H., Mangino, Massimo, Prins, Bram P., Campbell, Archie, Li-Gao, Ruifang, Chauhan, Ganesh, Oldmeadow, Abecasis, Goncalo, Abedi, Maryam, Barbieri, Caterina M., Batini, Chiara, Blake, Tineka, Boehnke, Michael, Bottinger, Erwin P., Braund, Peter S., Brumat, Marco, Harry, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J., Damman, Jeffrey J., Davies, Gail, de Geus, Eco J., de Mutsert, Renee, Deelen, Joris, Demirkale, Yusuf, Doney, Alex S. F., Dorr, Marcus, Ferreira, Teresa, Franberg, Mattias, Giedraitis, Vilmantas, Gieger, Christian, Giulianini, Franco, Gow, Alan J., Hamsten, Anders, Tamara B., Hofman, Albert, Holliday, Elizabeth G., Jarvelin, Marjo-Riitta, Johansson, Asa, Johnson, Andrew D., Jousilahti, Pekka, Jula, Antti, Kahonen, Mika, Kathiresan, Sekar, Khaw, Kay-Tee, Kolcic, Ivana, Koskinen, Seppo, Langenberg, Claudia, Larson, Marty, Launer, Lenore J., Lehne, Benjamin, Liewald, David C. M., Lin, Lind, Lars, Mach, Francois, Mamasoula, Chrysovalanto, Menni, Cristina, Milaneschi, Yuri, Morgan, Anna, Morrison, Alanna C., Munson, Nandakumar, Priyanka, Quang Tri Nguyen, Nutile, Oldehinkel, Albertine J., Oostra, Ben A., Org, Elin, Palotie, Aarno, Pare, Guillaume, Pattie, Alison, Penninx, Brenda W. J. H., Pramstaller, Peter P., Raitakari, Olli T., Rice, Kenneth, Ridker, Paul M., Riese, Harriette, Ripatti, Samuli, Robino, Antonietta, Rotter, Jerome I., Rudan, Igor, Saba, Yasaman, Saint Pierre, Aude, Sala, Cinzia F., Sarin, Antti-Pekka, Schmidt, Reinhold, Scott, Rodney, Seelen, Marc A., Siscovick, Sorice, Rossella, Stott, David J., Sundstrom, Johan, Swertz, Taylor, Kent D., Tzourio, Christophe, Uitterlinden, Andre G., Volker, Uwe, Vollenweider, Wild, Sarah, Willemsen, Gonneke, Wright, Alan F., Yao, Jie, Theriault, Sebastien, Conen, Attia, Debette, Stephanie, 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, Cecila M., Vitart, Veronique, Tuomilehto, Jaakko, Gyllensten, Ulf, Knekt, Deary, Ian J., Ciullo, Marina, Elosua, Roberto, Bernard D., Hicks, Andrew A., Robert A., Gasparini, Paolo, Laan, YongMei, Watkins, Hugh, Hartman, Catharina A., Salomaa, Veikko, Toniolo, Perola, Markus, Wilson, James F., Helena, Zhao, Jing Hua, Lehtimaki, 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., Oscar H., Bochud, Murielle, Andrew P., Int Consortium Blood Pressure ICBP, CHD Exome Consortium, ExomeBP Consortium, T2D-GENES Consortium, GoT2D Genes Consortium, CHARGE BP Exome Consortium, iGEN-BP Consortium, UK Biobank CardioMetab Consortium, BIOS Consortium, Lifelines Cohort Study, Understanding Soc Sci Grp, UK Biobank, National Institute for Health Research, Imperial College Healthcare NHS Trust- BRC Funding, British Heart Foundation, Medical Research Council (MRC), Lee Kong Chian School of Medicine (LKCMedicine), International Consortium of Blood Pressure (ICBP) 1000G Analyses, BIOS Consortium, Lifelines Cohort Study, Understanding Society Scientific group, CHD Exome+ Consortium, ExomeBP Consortium, T2D-GENES Consortium, GoT2DGenes Consortium, Cohorts for Heart and Ageing Research in Genome Epidemiology (CHARGE) BP Exome Consortium, International Genomics of Blood Pressure (iGEN-BP) Consortium, UK Biobank CardioMetabolic Consortium BP working group, Völker, U., Vollenweider, P., Wild, S., Willemsen, G., Wright, A.F., Yao, J., Thériault, S., Conen, D., John, A., Sever, P., Debette, S., Mook-Kanamori, D.O., Zeggini, E., Spector, T.D., van der Harst, P., Palmer, C.N., Vergnaud, A.C., Loos, R.J., Polasek, O., Starr, J.M., Girotto, G., Hayward, C., Kooner, J.S., Lindgren, C.M., Vitart, V., Samani, N.J., Tuomilehto, J., Gyllensten, U., Knekt, P., Deary, I.J., Ciullo, M., Elosua, R., Keavney, B.D., Hicks, A.A., Scott, R.A., Gasparini, P., Laan, M., Liu, Y., Watkins, H., Hartman, C.A., Salomaa, V., Toniolo, D., Perola, M., Wilson, J.F., Schmidt, H., Zhao, J.H., Lehtimäki, T., van Duijn, C.M., Gudnason, V., Psaty, B.M., Peters, A., Rettig, R., James, A., Jukema, J.W., Strachan, D.P., Palmas, W., Metspalu, A., Ingelsson, E., Boomsma, D.I., Franco, O.H., Bochud, M., Newton-Cheh, C., Munroe, P.B., Elliott, P., Chasman, D.I., Chakravarti, A., Knight, J., Morris, A.P., Levy, D., Tobin, M.D., Snieder, H., Caulfield, M.J., Ehret, G.B., Barnes, M.R., Tzoulaki, I., Warren, Helen R., Evangelou, Evangelo, Cabrera, Claudia P., Gao, He, Ren, Meixia, Mifsud, Borbala, Ntalla, Ioanna, Surendran, Praveen, Liu, Chunyu, Cook, James P., Kraja, Aldi T., Drenos, Fotio, 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, Mari, Poulter, Neil, Farrall, Martin, Gansevoort, Ron T., Padmanabhan, Sandosh, Magi, Reedik, Stanton, Alice, Connell, John, Bakker, Stephan J. L., Metspalu, Andre, Shields, Denis C., Thom, Simon, Brown, Morri, Sever, Peter, Esko, Tonu, Hayward, Caroline, van der Harst, Pim, Saleheen, Danish, Chowdhury, Rajiv, Chambers, John C, 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., Barnes, Michael R., Tzoulaki, Joanna, Caulfield, Mark J., Elliott, Paul, 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., 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., Lyytikainen, Leo Pekka, Mahajan, Anubha, Wareham, Nicholas J., Hofer, Edith, Joshi, Peter K., Kristiansson, Kati, Traglia, Michela, Havulinna, Aki S., Goel, Anuj, Nalls, Mike A., Sober, Siim, Vuckovic, Dragana, Luan, Jian'An, Del Greco M, Fabiola, 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, Goncalo, Abedi, Maryam, Barbieri, Caterina M., Batini, Chiara, Blake, Tineka, Boehnke, Michael, Bottinger, Erwin P., Braund, Peter S., Brown, Morris), Brumat, Marco, Campbell, Harry, Chambers, John C., Cocca, Massimiliano, Collins, Franci, Connell, John), Cordell, Heather J., Damman, Jeffrey J., Davies, Gail, de Geus, Eco J., de Mutsert, Renee, Deelen, Jori, Demirkale, Yusuf, Doney, Alex S. F., Dorr, Marcu, Ferreira, Teresa, Franberg, Mattia, Giedraitis, Vilmanta, Gieger, Christian, Giulianini, Franco, Gow, Alan J., Hamsten, Ander, Harris, Tamara B., Hofman, Albert, Holliday, Elizabeth G., Jarvelin, Marjo Riitta, Johansson, Asa, Johnson, Andrew D., Jousilahti, Pekka, Jula, Antti, Kahonen, 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, Lar, Mach, Francoi, Mamasoula, Chrysovalanto, Menni, Cristina, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew D., Morrison, Alanna C., Munson, Peter J., Nandakumar, Priyanka, Quang Tri, Nguyen, Nutile, Teresa, Oldehinkel, Albertine J., Oostra, Ben A., Org, Elin, Palotie, Aarno, Pare, Guillaume, Pattie, Alison, Penninx, Brenda W. J. H., Pramstaller, Peter P., Raitakari, Olli T., Rice, Kenneth, Ridker, Paul M., Riese, Harriette, Ripatti, Samuli, Robino, Antonietta, Rotter, Jerome I., Rudan, Igor, Saba, Yasaman, Saint Pierre, Aude, Sala, Cinzia F., Sarin, Antti Pekka, Schmidt, Reinhold, Scott, Rodney, Seelen, Marc A., Siscovick, David, Sorice, Rossella, Stott, David J., Sundstrom, Johan, Swertz, Morri, Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre G., Volker, Uwe, Vollenweider, Peter, Wild, Sarah, Willemsen, Gonneke, Wright, Alan F., Yao, Jie, Theriault, Sebastien, Conen, David, John, Attia, Debette, Stephanie, 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, Gyllensten, Ulf, Knekt, Paul, Deary, Ian J., Ciullo, Marina, Elosua, Roberto, Keavney, Bernard D., Hicks, Andrew A., Scott, Robert A., Gasparini, Paolo, Laan, Mari, Liu, Yongmei, Watkins, Hugh, Hartman, Catharina A., Salomaa, Veikko, Toniolo, Daniela, Perola, Marku, Wilson, James F., Schmidt, Helena, Zhao, Jing Hua, Lehtimaki, 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, Morris, Andrew P., Tobin, Martin D, CHD Exome, Consortium, Exomebp, Consortium, T2D GENES, Consortium, GoT2D Genes, Consortium, CHARGE BP Exome, Consortium, iGEN BP, Consortium, UK Biobank CardioMetab, Consortium, Bios, Consortium, Lifelines Cohort, Study, Understanding Soc Sci, Grp, Pathology, Gastroenterology & Hepatology, Cardiology, Epidemiology, Internal Medicine, Clinical Genetics, Internal medicine, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Methodology, Surendran, Praveen [0000-0002-4911-6077], Marten, Jonathan [0000-0001-6916-2014], Chowdhury, Rajiv [0000-0003-4881-5690], Howson, Joanna [0000-0001-7618-0050], and Apollo - University of Cambridge Repository
- Subjects
Netherlands Twin Register (NTR) ,Male ,0301 basic medicine ,Blood Pressure ,Genome-wide association study ,Disease ,Bioinformatics ,Risk Factors ,NADPH OXIDASE ,health care economics and organizations ,IN-VIVO ,11 Medical And Health Sciences ,Middle Aged ,Biobank ,3. Good health ,Pulse pressure ,ENDOTHELIAL-CELL ,Cardiovascular Diseases ,Hypertension ,CORONARY-ARTERY-DISEASE ,Medical genetics ,Female ,KEY ROLE ,Adult ,medicine.medical_specialty ,NEUROTROPHIC FACTOR ,HYPERTENSION ,COMMON ,GENE ,NOX4 ,METAANALYSIS ,INHIBITION ,European Continental Ancestry Group ,Biology ,Polymorphism, Single Nucleotide ,White People ,Article ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,UK BIOBANK ,Journal Article ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Risk factor ,Genetic association ,ta1184 ,ta3121 ,06 Biological Sciences ,030104 developmental biology ,Blood pressure ,MYOCARDIAL-INFARCTION ,Genetic Loci ,genome-wide association studies ,Genome-Wide Association Study ,Cardiovascular Risk ,Developmental Biology - Abstract
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 lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.
- Published
- 2017