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45 results on '"Theriault, Sebastien"'

1. Polygenic inheritance and its interplay with smoking history in predicting lung cancer diagnosis: a French-Canadian case-control cohort

Author

Boumtje, Véronique, Manikpurage, Hasanga D., Li, Zhonglin, Gaudreault, Nathalie, Armero, Victoria Saavedra, Boudreau, Dominique K., Renaut, Sébastien, Henry, Cyndi, Racine, Christine, Eslami, Aida, Bougeard, Stéphanie, Vigneau, Evelyne, Morissette, Mathieu, Arsenault, Benoit J., Labbé, Catherine, Laliberté, Anne-Sophie, Martel, Simon, Maltais, François, Couture, Christian, Desmeules, Patrice, Mathieu, Patrick, Thériault, Sébastien, Joubert, Philippe, and Bossé, Yohan

Published
2024
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3. Prioritization of Kidney Cell Types Highlights Myofibroblast Cells in Regulating Human Blood Pressure

Author

Evangelou, Evangelos, Warren, Helen R., Gao, He, Ntritsos, Georgios, Dimou, Niki, Esko, Tonu, Mägi, Reedik, Milani, Lili, Almgren, Peter, Boutin, Thibaud, Debette, Stéphanie, Ding, Jun, Giulianini, Franco, Holliday, Elizabeth G., Jackson, Anne U., Li -Gao, Ruifang, Lin, Wei -Yu, Luan, Jian'an, Mangino, Massimo, Oldmeadow, Christopher, Prins, Bram Peter, Qian, Yong, Sargurupremraj, Muralidharan, Shah, Nabi, Surendran, Praveen, Thériault, Sébastien, Verweij, Niek, Willems, Sara M., Zhao, Jing -Hua, Amouyel, Philippe, Connell, John, de Mutsert, Renée, Doney, Alex S.F., Farrall, Martin, Menni, Cristina, Morris, Andrew D., Noordam, Raymond, Paré, Guillaume, Poulter, Neil R., Shields, Denis C., Stanton, Alice, Thom, Simon, Abecasis, Gonçalo, Amin, Najaf, Arking, Dan E., Ayers, Kristin L., Barbieri, Caterina M., Batini, Chiara, Bis, Joshua C., Blake, Tineka, Bochud, Murielle, Boehnke, Michael, Boerwinkle, Eric, Boomsma, Dorret I., Bottinger, Erwin P., Braund, Peter S., Brumat, Marco, Campbell, Archie, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C., Chauhan, Ganesh, Ciullo, Marina, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J., Davies, Gail, de Borst, Martin H., de Geus, Eco J., Deary, Ian J., Deelen, Joris, Del Greco M, Fabiola, Demirkale, Cumhur Yusuf, Dörr, Marcus, Ehret, Georg B., Elosua, Roberto, Enroth, Stefan, Erzurumluoglu, A. Mesut, Ferreira, Teresa, Frånberg, Mattias, Franco, Oscar H., Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Goel, Anuj, Gow, Alan J., Gudnason, Vilmundur, Guo, Xiuqing, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B., Harris, Sarah E., Hartman, Catharina A., Havulinna, Aki S., Hicks, Andrew A., Hofer, Edith, Hofman, Albert, Hottenga, Jouke-Jan, Huffman, Jennifer E., Hwang, Shih-Jen, Ingelsson, Erik, James, Alan, Jansen, Rick, Jarvelin, Marjo -Riitta, Joehanes, Roby, Johansson, Åsa, Johnson, Andrew D., Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Keavney, Bernard D., Khaw, Kay-Tee, Knekt, Paul, Knight, Joanne, Kolcic, Ivana, Kooner, Jaspal S., Koskinen, Seppo, Kristiansson, Kati, Kutalik, Zoltan, Laan, Maris, Larson, Marty, Launer, Lenore J., Lehne, Benjamin, Lehtimäki, Terho, Liewald, David C.M., Lin, Li, Lind, Lars, Lindgren, Cecilia M., Liu, YongMei, Loos, Ruth J.F., Lopez, Lorna M., Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamasoula, Chrysovalanto, Marrugat, Jaume, Marten, Jonathan, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew P., Morrison, Alanna C., Munson, Peter J., Nalls, Mike A., Nandakumar, Priyanka, Nelson, Christopher P., Niiranen, Teemu, Nolte, Ilja M., Nutile, Teresa, Oldehinkel, Albertine J., Oostra, Ben A., O'Reilly, Paul F., Org, Elin, Padmanabhan, Sandosh, Palmas, Walter, Palotie, Aarno, Pattie, Alison, Penninx, Brenda W.J.H., Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P., Nguyen, Quang Tri, Raitakari, Olli T., Rettig, Rainer, Rice, Kenneth, Ridker, Paul M., Ried, Janina S., Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rose, Lynda M., Rotter, Jerome I., Rudan, Igor, Ruggiero, Daniela, Saba, Yasaman, Sala, Cinzia F., Salomaa, Veikko, Samani, Nilesh J., Sarin, Antti-Pekka, Schmidt, Reinhold, Schmidt, Helena, Shrine, Nick, Siscovick, David, Smith, Albert V., Snieder, Harold, Sõber, Siim, Sorice, Rossella, Starr, John M., Stott, David J., Strachan, David P., Strawbridge, Rona J., Sundström, Johan, Swertz, Morris A., Taylor, Kent D., Teumer, Alexander, Tobin, Martin D., Tomaszewski, Maciej, Toniolo, Daniela, Traglia, Michela, Trompet, Stella, Tuomilehto, Jaakko, Tzourio, Christophe, Uitterlinden, André G., Vaez, Ahmad, van der Most, Peter J., van Duijn, Cornelia M., Verwoert, Germaine C., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Vuckovic, Dragana, Watkins, Hugh, Wild, Sarah H., Willemsen, Gonneke, Wilson, James F., Wright, Alan F., Yao, Jie, Zemunik, Tatijana, Zhang, Weihua, Attia, John R., Butterworth, Adam S., Chasman, Daniel I., Conen, David, Cucca, Francesco, Danesh, John, Hayward, Caroline, Howson, Joanna M.M., Laakso, Markku, Lakatta, Edward G., Langenberg, Claudia, Melander, Olle, Mook-Kanamori, Dennis O., Palmer, Colin N.A., Risch, Lorenz, Scott, Robert A., Scott, Rodney J., Sever, Peter, Spector, Tim D., van der Harst, Pim, Wareham, Nicholas J., Zeggini, Eleftheria, Levy, Daniel, Munroe, Patricia B., Newton-Cheh, Christopher, Brown, Morris J., Metspalu, Andres, Psaty, Bruce M., Wain, Louise V., Elliott, Paul, Caulfield, Mark J., Ganji-Arjenaki, Mahboube, Kamali, Zoha, Sardari, Soroush, and de Borst, Martin

Published
2024
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9. Genome-wide analyses identify SCN5A as a susceptibility locus for premature atrial contraction frequency

Author

Thériault, Sébastien, Imboden, Medea, Biggs, Mary L., Austin, Thomas R., Aeschbacher, Stefanie, Schaffner, Emmanuel, Brody, Jennifer A., Bartz, Traci M., Risch, Martin, Grossmann, Kirsten, Lin, Henry J., Soliman, Elsayed Z., Post, Wendy S., Risch, Lorenz, Krieger, Jose E., Pereira, Alexandre C., Heckbert, Susan R., Sotoodehnia, Nona, Probst-Hensch, Nicole M., and Conen, David

Published
2022
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13. Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease

Author

Ghodsian, Nooshin, Abner, Erik, Emdin, Connor A., Gobeil, Émilie, Taba, Nele, Haas, Mary E., Perrot, Nicolas, Manikpurage, Hasanga D., Gagnon, Éloi, Bourgault, Jérôme, St-Amand, Alexis, Couture, Christian, Mitchell, Patricia L., Bossé, Yohan, Mathieu, Patrick, Vohl, Marie-Claude, Tchernof, André, Thériault, Sébastien, Khera, Amit V., Esko, Tõnu, and Arsenault, Benoit J.

Published
2021
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14. A false-positive troponin assay leading to the misdiagnosis of myopericarditis

Author

Lague, Marianne, Turgeon, Pierre Yves, Theriault, Sebastien, and Steinberg, Christian

Subjects
Heart diseases -- Case studies -- Diagnosis, False positive reactions -- Case studies, Pericarditis -- Case studies -- Diagnosis, Cardiomyopathy -- Case studies -- Diagnosis, Health
Abstract

A 16-year-old girl who was an avid triathlete was transferred to our hospital with a working diagnosis of persistent myopericarditis. Her medical history was unremarkable and she had not received [...]

Published
2022
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19. Genetic and In Vitro Inhibition of PCSK9 and Calcific Aortic Valve Stenosis

Author

Perrot, Nicolas, Valerio, Vincenza, Moschetta, Donato, Boekholdt, S. Matthijs, Dina, Christian, Chen, Hao Yu, Abner, Erik, Martinsson, Andreas, Manikpurage, Hasanga D., Rigade, Sidwell, Capoulade, Romain, Mass, Elvira, Clavel, Marie-Annick, Le Tourneau, Thierry, Messika-Zeitoun, David, Wareham, Nicholas J., Engert, James C., Polvani, Gianluca, Pibarot, Philippe, Esko, Tõnu, Smith, J. Gustav, Mathieu, Patrick, Thanassoulis, George, Schott, Jean-Jacques, Bossé, Yohan, Camera, Marina, Thériault, Sébastien, Poggio, Paolo, and Arsenault, Benoit J.

Published
2020
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29. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author

Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B., Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.

Abstract

The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.

Published
2022
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30. Mendelian randomization analysis identifies blood tyrosine levels as a biomarker of non-alcoholic fatty liver disease

Author

Gobeil, Emilie, primary, Maltais-Payette, Ina, additional, Taba, Nele, additional, Briere, Francis, additional, Ghodsian, Nooshin, additional, Abner, Erik, additional, Bourgault, Jerome, additional, Gagnon, Eloi, additional, Manikpurage, Hasanga D., additional, Couture, Christian, additional, Mitchell, Patricia L., additional, Mathieu, Patrick, additional, Julien, Francois, additional, Corbeil, Jacques, additional, Vohl, Marie-Claude, additional, Theriault, Sebastien, additional, Esko, Tonu, additional, Tchernof, Andre, additional, and Arsenault, Benoit J., additional

Published
2021
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31. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author

Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.

Abstract

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

Published
2020
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32. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Author

Surendran, Praveen, Feofanova, Elena V., Lahrouchi, Najim, Ntalla, Ioanna, Karthikeyan, Savita, Cook, James, Chen, Lingyan, Mifsud, Borbala, Yao, Chen, Kraja, Aldi T., Cartwright, James H., Hellwege, Jacklyn N., Giri, Ayush, Tragante, Vinicius, Thorleifsson, Gudmar, Liu, Dajiang J., Prins, Bram P., Stewart, Isobel D., Cabrera, Claudia P., Eales, James M., Akbarov, Artur, Auer, Paul L., Bielak, Lawrence F., Bis, Joshua C., Braithwaite, Vickie S., Brody, Jennifer A., Daw, E. Warwick, Warren, Helen R., Drenos, Fotios, Nielsen, Sune Fallgaard, Faul, Jessica D., Fauman, Eric B., Fava, Cristiano, Ferreira, Teresa, Foley, Christopher N., Franceschini, Nora, Gao, He, Giannakopoulou, Olga, Giulianini, Franco, Gudbjartsson, Daniel F., Guo, Xiuqing, Harris, Sarah E., Havulinna, Aki S., Helgadottir, Anna, Huffman, Jennifer E., Hwang, Shih-Jen, Kanoni, Stavroula, Kontto, Jukka, Larson, Martin G., Li-Gao, Ruifang, Lindstrom, Jaana, Lotta, Luca A., Lu, Yingchang, Luan, Jian'an, Mahajan, Anubha, Malerba, Giovanni, Masca, Nicholas G. D., Mei, Hao, Menni, Cristina, Mook-Kanamori, Dennis O., Mosen-Ansorena, David, Muller-Nurasyid, Martina, Pare, Guillaume, Paul, Dirk S., Perola, Markus, Poveda, Alaitz, Rauramaa, Rainer, Richard, Melissa, Richardson, Tom G., Sepulveda, Nuno, Sim, Xueling, Smith, Albert, V, Smith, Jennifer A., Staley, James R., Stanakova, Alena, Sulem, Patrick, Theriault, Sebastien, Thorsteinsdottir, Unnur, Trompet, Stella, Varga, Tibor V., Edwards, Digna R. Velez, Veronesi, Giovanni, Weiss, Stefan, Willems, Sara M., Yao, Jie, Young, Robin, Yu, Bing, Zhang, Weihua, Zhao, Jing-Hua, Zhao, Wei, Evangelou, Evangelos, Aeschbacher, Stefanie, Asllanaj, Eralda, Blankenberg, Stefan, Bonnycastle, Lori L., Bork-Jensen, Jette, Brandslund, Ivan, Braund, Peter S., Burgess, Stephen, Cho, Kelly, Christensen, Cramer, Connell, John, de Mutsert, Renee, Dominiczak, Anna F., Dorr, Marcus, Eiriksdottir, Gudny, Farmaki, Aliki-Eleni, Gaziano, J. Michael, Grarup, Niels, Grove, Megan L., Hallmans, Göran, Hansen, Torben, Have, Christian T., Heiss, Gerardo, Jorgensen, Marit E., Jousilahti, Pekka, Kajantie, Eero, Kamat, Mihir, Karajamaki, AnneMari, Karpe, Fredrik, Koistinen, Heikki A., Kovesdy, Csaba P., Kuulasmaa, Kari, Laatikainen, Tiina, Lannfelt, Lars, Lee, I-Te, Lee, Wen-Jane, Linneberg, Allan, Martin, Lisa W., Moitry, Marie, Nadkarni, Girish, Neville, Matt J., Palmer, Colin N. A., Papanicolaou, George J., Pedersen, Oluf, Peters, James, Poulter, Neil, Rasheed, Asif, Rasmussen, Katrine L., Rayner, N. William, Magi, Reedik, Renström, Frida, Rettig, Rainer, Rossouw, Jacques, Schreiner, Pamela J., Sever, Peter S., Sigurdsson, Emil L., Skaaby, Tea, Sun, Yan, V, Sundstrom, Johan, Thorgeirsson, Gudmundur, Esko, Tonu, Trabetti, Elisabetta, Tsao, Philip S., Tuomi, Tiinamaija, Turner, Stephen T., Tzoulaki, Ioanna, Vaartjes, Ilonca, Vergnaud, Anne-Claire, Willer, Cristen J., Wilson, Peter W. F., Witte, Daniel R., Yonova-Doing, Ekaterina, Zhang, He, Aliya, Naheed, Almgren, Peter, Amouyel, Philippe, Asselbergs, Folkert W., Barnes, Michael R., Blakemore, Alexandra, I, Boehnke, Michael, Bots, Michiel L., Bottinger, Erwin P., Buring, Julie E., Chambers, John C., Chen, Yii-Der Ida, Chowdhury, Rajiv, Conen, David, Correa, Adolfo, Smith, George Davey, de Boer, Rudolf A., Deary, Ian J., Dedoussis, George, Deloukas, Panos, Di Angelantonio, Emanuele, Elliott, Paul, Felix, Stephan B., Ferrieres, Jean, Ford, Ian, Fornage, Myriam, Franks, Paul W., Franks, Stephen, Frossard, Philippe, Gambaro, Giovanni, Gaunt, Tom R., Groop, Leif, Gudnason, Vilmundur, Harris, Tamara B., Hayward, Caroline, Hennig, Branwen J., Herzig, Karl-Heinz, Ingelsson, Erik, Tuomilehto, Jaakko, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kardia, Sharon L. R., Kee, Frank, Kooner, Jaspal S., Kooperberg, Charles, Launer, Lenore J., Lind, Lars, Loos, Ruth J. F., Majumder, Abdulla Al Shafi, Laakso, Markku, McCarthy, Mark, I, Melander, Olle, Mohlke, Karen L., Murray, Alison D., Nordestgaard, Borge Gronne, Orho-Melander, Marju, Packard, Chris J., Padmanabhan, Sandosh, Palmas, Walter, Polasek, Ozren, Porteous, David J., Prentice, Andrew M., Province, Michael A., Relton, Caroline L., Rice, Kenneth, Ridker, Paul M., Rolandsson, Olov, Rosendaal, Frits R., Rotter, Jerome, I, Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Sattar, Naveed, Sheu, Wayne H-H, Smith, Blair H., Soranzo, Nicole, Spector, Timothy D., Starr, John M., Sebert, Sylvain, Taylor, Kent D., Lakka, Timo A., Timpson, Nicholas J., Tobin, Martin D., van der Harst, Pim, van der Meer, Peter, Ramachandran, Vasan S., Verweij, Niek, Virtamo, Jarmo, Volker, Uwe, Weir, David R., Zeggini, Eleftheria, Charchar, Fadi J., Wareham, Nicholas J., Langenberg, Claudia, Tomaszewski, Maciej, Butterworth, Adam S., Caulfield, Mark J., Danesh, John, Edwards, Todd L., Holm, Hilma, Hung, Adriana M., Lindgren, Cecilia M., Liu, Chunyu, Manning, Alisa K., Morris, Andrew P., Morrison, Alanna C., O'Donnell, Christopher J., Psaty, Bruce M., Saleheen, Danish, Stefansson, Kari, Boerwinkle, Eric, Chasman, Daniel, I, Levy, Daniel, Newton-Cheh, Christopher, Munroe, Patricia B., Howson, Joanna M. M., Surendran, Praveen, Feofanova, Elena V., Lahrouchi, Najim, Ntalla, Ioanna, Karthikeyan, Savita, Cook, James, Chen, Lingyan, Mifsud, Borbala, Yao, Chen, Kraja, Aldi T., Cartwright, James H., Hellwege, Jacklyn N., Giri, Ayush, Tragante, Vinicius, Thorleifsson, Gudmar, Liu, Dajiang J., Prins, Bram P., Stewart, Isobel D., Cabrera, Claudia P., Eales, James M., Akbarov, Artur, Auer, Paul L., Bielak, Lawrence F., Bis, Joshua C., Braithwaite, Vickie S., Brody, Jennifer A., Daw, E. Warwick, Warren, Helen R., Drenos, Fotios, Nielsen, Sune Fallgaard, Faul, Jessica D., Fauman, Eric B., Fava, Cristiano, Ferreira, Teresa, Foley, Christopher N., Franceschini, Nora, Gao, He, Giannakopoulou, Olga, Giulianini, Franco, Gudbjartsson, Daniel F., Guo, Xiuqing, Harris, Sarah E., Havulinna, Aki S., Helgadottir, Anna, Huffman, Jennifer E., Hwang, Shih-Jen, Kanoni, Stavroula, Kontto, Jukka, Larson, Martin G., Li-Gao, Ruifang, Lindstrom, Jaana, Lotta, Luca A., Lu, Yingchang, Luan, Jian'an, Mahajan, Anubha, Malerba, Giovanni, Masca, Nicholas G. D., Mei, Hao, Menni, Cristina, Mook-Kanamori, Dennis O., Mosen-Ansorena, David, Muller-Nurasyid, Martina, Pare, Guillaume, Paul, Dirk S., Perola, Markus, Poveda, Alaitz, Rauramaa, Rainer, Richard, Melissa, Richardson, Tom G., Sepulveda, Nuno, Sim, Xueling, Smith, Albert, V, Smith, Jennifer A., Staley, James R., Stanakova, Alena, Sulem, Patrick, Theriault, Sebastien, Thorsteinsdottir, Unnur, Trompet, Stella, Varga, Tibor V., Edwards, Digna R. Velez, Veronesi, Giovanni, Weiss, Stefan, Willems, Sara M., Yao, Jie, Young, Robin, Yu, Bing, Zhang, Weihua, Zhao, Jing-Hua, Zhao, Wei, Evangelou, Evangelos, Aeschbacher, Stefanie, Asllanaj, Eralda, Blankenberg, Stefan, Bonnycastle, Lori L., Bork-Jensen, Jette, Brandslund, Ivan, Braund, Peter S., Burgess, Stephen, Cho, Kelly, Christensen, Cramer, Connell, John, de Mutsert, Renee, Dominiczak, Anna F., Dorr, Marcus, Eiriksdottir, Gudny, Farmaki, Aliki-Eleni, Gaziano, J. Michael, Grarup, Niels, Grove, Megan L., Hallmans, Göran, Hansen, Torben, Have, Christian T., Heiss, Gerardo, Jorgensen, Marit E., Jousilahti, Pekka, Kajantie, Eero, Kamat, Mihir, Karajamaki, AnneMari, Karpe, Fredrik, Koistinen, Heikki A., Kovesdy, Csaba P., Kuulasmaa, Kari, Laatikainen, Tiina, Lannfelt, Lars, Lee, I-Te, Lee, Wen-Jane, Linneberg, Allan, Martin, Lisa W., Moitry, Marie, Nadkarni, Girish, Neville, Matt J., Palmer, Colin N. A., Papanicolaou, George J., Pedersen, Oluf, Peters, James, Poulter, Neil, Rasheed, Asif, Rasmussen, Katrine L., Rayner, N. William, Magi, Reedik, Renström, Frida, Rettig, Rainer, Rossouw, Jacques, Schreiner, Pamela J., Sever, Peter S., Sigurdsson, Emil L., Skaaby, Tea, Sun, Yan, V, Sundstrom, Johan, Thorgeirsson, Gudmundur, Esko, Tonu, Trabetti, Elisabetta, Tsao, Philip S., Tuomi, Tiinamaija, Turner, Stephen T., Tzoulaki, Ioanna, Vaartjes, Ilonca, Vergnaud, Anne-Claire, Willer, Cristen J., Wilson, Peter W. F., Witte, Daniel R., Yonova-Doing, Ekaterina, Zhang, He, Aliya, Naheed, Almgren, Peter, Amouyel, Philippe, Asselbergs, Folkert W., Barnes, Michael R., Blakemore, Alexandra, I, Boehnke, Michael, Bots, Michiel L., Bottinger, Erwin P., Buring, Julie E., Chambers, John C., Chen, Yii-Der Ida, Chowdhury, Rajiv, Conen, David, Correa, Adolfo, Smith, George Davey, de Boer, Rudolf A., Deary, Ian J., Dedoussis, George, Deloukas, Panos, Di Angelantonio, Emanuele, Elliott, Paul, Felix, Stephan B., Ferrieres, Jean, Ford, Ian, Fornage, Myriam, Franks, Paul W., Franks, Stephen, Frossard, Philippe, Gambaro, Giovanni, Gaunt, Tom R., Groop, Leif, Gudnason, Vilmundur, Harris, Tamara B., Hayward, Caroline, Hennig, Branwen J., Herzig, Karl-Heinz, Ingelsson, Erik, Tuomilehto, Jaakko, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kardia, Sharon L. R., Kee, Frank, Kooner, Jaspal S., Kooperberg, Charles, Launer, Lenore J., Lind, Lars, Loos, Ruth J. F., Majumder, Abdulla Al Shafi, Laakso, Markku, McCarthy, Mark, I, Melander, Olle, Mohlke, Karen L., Murray, Alison D., Nordestgaard, Borge Gronne, Orho-Melander, Marju, Packard, Chris J., Padmanabhan, Sandosh, Palmas, Walter, Polasek, Ozren, Porteous, David J., Prentice, Andrew M., Province, Michael A., Relton, Caroline L., Rice, Kenneth, Ridker, Paul M., Rolandsson, Olov, Rosendaal, Frits R., Rotter, Jerome, I, Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Sattar, Naveed, Sheu, Wayne H-H, Smith, Blair H., Soranzo, Nicole, Spector, Timothy D., Starr, John M., Sebert, Sylvain, Taylor, Kent D., Lakka, Timo A., Timpson, Nicholas J., Tobin, Martin D., van der Harst, Pim, van der Meer, Peter, Ramachandran, Vasan S., Verweij, Niek, Virtamo, Jarmo, Volker, Uwe, Weir, David R., Zeggini, Eleftheria, Charchar, Fadi J., Wareham, Nicholas J., Langenberg, Claudia, Tomaszewski, Maciej, Butterworth, Adam S., Caulfield, Mark J., Danesh, John, Edwards, Todd L., Holm, Hilma, Hung, Adriana M., Lindgren, Cecilia M., Liu, Chunyu, Manning, Alisa K., Morris, Andrew P., Morrison, Alanna C., O'Donnell, Christopher J., Psaty, Bruce M., Saleheen, Danish, Stefansson, Kari, Boerwinkle, Eric, Chasman, Daniel, I, Levy, Daniel, Newton-Cheh, Christopher, Munroe, Patricia B., and Howson, Joanna M. M.

Abstract

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets., Errata: Surendran, P., Feofanova, E.V., Lahrouchi, N. et al. Publisher Correction: Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals. Nature Genetics 53, 762 (2021). https://doi.org/10.1038/s41588-021-00832-z

Published
2020
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33. A Trans-Omic Mendelian Randomization Study of Parental Lifespan Uncovers Novel Aging Biology and Drug Candidates for Human Healthspan Extension

Author

Perrot, Nicolas, primary, Pelletier, William, additional, Bourgeault, Jerome, additional, Couture, Christian, additional, Li, Zhonglin, additional, Mitchell, Patricia, additional, Ghodsian, Nooshin, additional, Bosse, Yohan, additional, Theriault, Sebastien, additional, Mathieu, Patrick, additional, and Arsenault, Benoit J, additional

Published
2020
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34. Multi-ethnic genome-wide association study for atrial fibrillation

Author

Roselli, Carolina, Chaffin, Mark D., Weng, Lu-Chen, Aeschbacher, Stefanie, Ahlberg, Gustav, Albert, Christine M., Almgren, Peter, Alonso, Alvaro, Anderson, Christopher D., Aragam, Krishna G., Arking, Dan E., Barnard, John, Bartz, Traci M., Benjamin, Emelia J., Bihlmeyer, Nathan A., Bis, Joshua C., Bloom, Heather L., Boerwinkle, Eric, Bottinger, Erwin B., Brody, Jennifer A., Calkins, Hugh, Campbell, Archie, Cappola, Thomas P., Carlquist, John, Chasman, Daniel I., Chen, Lin Y., Chen, Yii-Der Ida, Choi, Eue-Keun, Choi, Seung Hoan, Christophersen, Ingrid E., Chung, Mina K., Cole, John W., Conen, David, Cook, James, Crijns, Harry J., Cutler, Michael J., Damrauer, Scott M., Daniels, Brian R., Darbar, Dawood, Delgado, Graciela, Denny, Joshua C., Dichgans, Martin, Doerr, Marcus, Dudink, Elton A., Dudley, Samuel C., Esa, Nada, Esko, Tonu, Eskola, Markku, Fatkin, Diane, Felix, Stephan B., Ford, Ian, Franco, Oscar H., Geelhoed, Bastiaan, Grewal, Raji P., Gudnason, Vilmundur, Guo, Xiuqing, Gupta, Namrata, Gustafsson, Stefan, Gutmann, Rebecca, Hamsten, Anders, Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Hernesniemi, Jussi, Hocking, Lynne J., Hofman, Albert, Horimoto, Andrea R. V. R., Huang, Jie, Huang, Paul L., Huffman, Jennifer, Ingelsson, Erik, Ipek, Esra Gucuk, Ito, Kaoru, Jimenez-Conde, Jordi, Johnson, Renee, Jukema, J. Wouter, Kaeaeb, Stefan, Kahonen, Mika, Kamatani, Yoichiro, Kane, John P., Kastrati, Adnan, Kathiresan, Sekar, Katschnig-Winter, Petra, Kavousi, Maryam, Kessler, Thorsten, Kietselaer, Bas L., Kirchhof, Paulus, Kleber, Marcus E., Knight, Stacey, Krieger, Jose E., Kubo, Michiaki, Launer, Lenore J., Laurikka, Jari, Lehtimaki, Terho, Leineweber, Kirsten, Lemaitre, Rozenn N., Li, Man, Lim, Hong Euy, Lin, Henry J., Lin, Honghuang, Lind, Lars, Lindgren, Cecilia M., Lokki, Marja-Liisa, London, Barry, Loos, Ruth J. F., Low, Siew-Kee, Lu, Yingchang, Lyytikainen, Leo-Pekka, Macfarlane, Peter W., Magnusson, Patrik K., Mahajan, Anubha, Malik, Rainer, Mansur, Alfredo J., Marcus, Gregory M., Margolin, Lauren, Margulies, Kenneth B., Maerz, Winfried, McManus, David D., Melander, Olle, Mohanty, Sanghamitra, Montgomery, Jay A., Morley, Michael P., Morris, Andrew P., Mueller-Nurasyid, Martina, Natale, Andrea, Nazarian, Saman, Neumann, Benjamin, Newton-Cheh, Christopher, Niemeijer, Maartje N., Nikus, Kjell, Nilsson, Peter, Noordam, Raymond, Oellers, Heidi, Olesen, Morten S., Orho-Melander, Marju, Padmanabhan, Sandosh, Pak, Hui-Nam, Pare, Guillaume, Pedersen, Nancy L., Pera, Joanna, Pereira, Alexandre, Porteous, David, Psaty, Bruce M., Pulit, Sara L., Pullinger, Clive R., Rader, Daniel J., Refsgaard, Lena, Ribases, Marta, Ridker, Paul M., Rienstra, Michiel, Risch, Lorenz, Roden, Dan M., Rosand, Jonathan, Rosenberg, Michael A., Rost, Natalia, Rotter, Jerome I., Saba, Samir, Sandhu, Roopinder K., Schnabel, Renate B., Schramm, Katharina, Schunkert, Heribert, Schurman, Claudia, Scott, Stuart A., Seppala, Ilkka, Shaffer, Christian, Shah, Svati, Shalaby, Alaa A., Shim, Jaemin, Shoemaker, M. Benjamin, Siland, Joylene E., Sinisalo, Juha, Sinner, Moritz F., Slowik, Agnieszka, Smith, Albert V., Smith, Blair H., Smith, J. Gustav, Smith, Jonathan D., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Stricker, Bruno H., Sun, Albert, Sun, Han, Svendsen, Jesper H., Tanaka, Toshihiro, Tanriverdi, Kahraman, Taylor, Kent D., Teder-Laving, Maris, Teumer, Alexander, Theriault, Sebastien, Trompet, Stella, Tucker, Nathan R., Tveit, Arnljot, Uitterlinden, Andre G., Van Der Harst, Pim, Van Gelder, Isabelle C., Van Wagoner, David R., Verweij, Niek, Vlachopoulou, Efthymia, Voelker, Uwe, Wang, Biqi, Weeke, Peter E., Weijs, Bob, Weiss, Raul, Weiss, Stefan, Wells, Quinn S., Wiggins, Kerri L., Wong, Jorge A., Woo, Daniel, Worrall, Bradford B., Yang, Pil-Sung, Yao, Jie, Yoneda, Zachary T., Zeller, Tanja, Zeng, Lingyao, Lubitz, Steven A., Lunetta, Kathryn L., Ellinor, Patrick T., Roselli, Carolina, Chaffin, Mark D., Weng, Lu-Chen, Aeschbacher, Stefanie, Ahlberg, Gustav, Albert, Christine M., Almgren, Peter, Alonso, Alvaro, Anderson, Christopher D., Aragam, Krishna G., Arking, Dan E., Barnard, John, Bartz, Traci M., Benjamin, Emelia J., Bihlmeyer, Nathan A., Bis, Joshua C., Bloom, Heather L., Boerwinkle, Eric, Bottinger, Erwin B., Brody, Jennifer A., Calkins, Hugh, Campbell, Archie, Cappola, Thomas P., Carlquist, John, Chasman, Daniel I., Chen, Lin Y., Chen, Yii-Der Ida, Choi, Eue-Keun, Choi, Seung Hoan, Christophersen, Ingrid E., Chung, Mina K., Cole, John W., Conen, David, Cook, James, Crijns, Harry J., Cutler, Michael J., Damrauer, Scott M., Daniels, Brian R., Darbar, Dawood, Delgado, Graciela, Denny, Joshua C., Dichgans, Martin, Doerr, Marcus, Dudink, Elton A., Dudley, Samuel C., Esa, Nada, Esko, Tonu, Eskola, Markku, Fatkin, Diane, Felix, Stephan B., Ford, Ian, Franco, Oscar H., Geelhoed, Bastiaan, Grewal, Raji P., Gudnason, Vilmundur, Guo, Xiuqing, Gupta, Namrata, Gustafsson, Stefan, Gutmann, Rebecca, Hamsten, Anders, Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Hernesniemi, Jussi, Hocking, Lynne J., Hofman, Albert, Horimoto, Andrea R. V. R., Huang, Jie, Huang, Paul L., Huffman, Jennifer, Ingelsson, Erik, Ipek, Esra Gucuk, Ito, Kaoru, Jimenez-Conde, Jordi, Johnson, Renee, Jukema, J. Wouter, Kaeaeb, Stefan, Kahonen, Mika, Kamatani, Yoichiro, Kane, John P., Kastrati, Adnan, Kathiresan, Sekar, Katschnig-Winter, Petra, Kavousi, Maryam, Kessler, Thorsten, Kietselaer, Bas L., Kirchhof, Paulus, Kleber, Marcus E., Knight, Stacey, Krieger, Jose E., Kubo, Michiaki, Launer, Lenore J., Laurikka, Jari, Lehtimaki, Terho, Leineweber, Kirsten, Lemaitre, Rozenn N., Li, Man, Lim, Hong Euy, Lin, Henry J., Lin, Honghuang, Lind, Lars, Lindgren, Cecilia M., Lokki, Marja-Liisa, London, Barry, Loos, Ruth J. F., Low, Siew-Kee, Lu, Yingchang, Lyytikainen, Leo-Pekka, Macfarlane, Peter W., Magnusson, Patrik K., Mahajan, Anubha, Malik, Rainer, Mansur, Alfredo J., Marcus, Gregory M., Margolin, Lauren, Margulies, Kenneth B., Maerz, Winfried, McManus, David D., Melander, Olle, Mohanty, Sanghamitra, Montgomery, Jay A., Morley, Michael P., Morris, Andrew P., Mueller-Nurasyid, Martina, Natale, Andrea, Nazarian, Saman, Neumann, Benjamin, Newton-Cheh, Christopher, Niemeijer, Maartje N., Nikus, Kjell, Nilsson, Peter, Noordam, Raymond, Oellers, Heidi, Olesen, Morten S., Orho-Melander, Marju, Padmanabhan, Sandosh, Pak, Hui-Nam, Pare, Guillaume, Pedersen, Nancy L., Pera, Joanna, Pereira, Alexandre, Porteous, David, Psaty, Bruce M., Pulit, Sara L., Pullinger, Clive R., Rader, Daniel J., Refsgaard, Lena, Ribases, Marta, Ridker, Paul M., Rienstra, Michiel, Risch, Lorenz, Roden, Dan M., Rosand, Jonathan, Rosenberg, Michael A., Rost, Natalia, Rotter, Jerome I., Saba, Samir, Sandhu, Roopinder K., Schnabel, Renate B., Schramm, Katharina, Schunkert, Heribert, Schurman, Claudia, Scott, Stuart A., Seppala, Ilkka, Shaffer, Christian, Shah, Svati, Shalaby, Alaa A., Shim, Jaemin, Shoemaker, M. Benjamin, Siland, Joylene E., Sinisalo, Juha, Sinner, Moritz F., Slowik, Agnieszka, Smith, Albert V., Smith, Blair H., Smith, J. Gustav, Smith, Jonathan D., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Stricker, Bruno H., Sun, Albert, Sun, Han, Svendsen, Jesper H., Tanaka, Toshihiro, Tanriverdi, Kahraman, Taylor, Kent D., Teder-Laving, Maris, Teumer, Alexander, Theriault, Sebastien, Trompet, Stella, Tucker, Nathan R., Tveit, Arnljot, Uitterlinden, Andre G., Van Der Harst, Pim, Van Gelder, Isabelle C., Van Wagoner, David R., Verweij, Niek, Vlachopoulou, Efthymia, Voelker, Uwe, Wang, Biqi, Weeke, Peter E., Weijs, Bob, Weiss, Raul, Weiss, Stefan, Wells, Quinn S., Wiggins, Kerri L., Wong, Jorge A., Woo, Daniel, Worrall, Bradford B., Yang, Pil-Sung, Yao, Jie, Yoneda, Zachary T., Zeller, Tanja, Zeng, Lingyao, Lubitz, Steven A., Lunetta, Kathryn L., and Ellinor, Patrick T.

Abstract

Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.

Published
2018
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35. Genetic analysis of over one million people identifies 535 new loci associated with blood pressure traits

Author

Evangelou, Evangelos, Warren, Helen R., Mosen-Ansorena, David, Mifsud, Borbala, Pazoki, Raha, Gao, He, Ntritsos, Georgios, Dimou, Niki, Cabrera, Claudia, Karaman, Ibrahim, Ng, Fu Liang, Evangelou, Marina, Witkowska, Katarzyna, Tzanis, Evan, Hellwege, Jacklyn, Giri, Ayush, Edwards, Digna R. Velez, Sun, Yan V., Cho, Kelly, Gaziano, J. Michael, Wilson, Peter W.F., Tsao, Philip S., Kovesdy, Csaba P., Esko, Tonu, Magi, Reedik, Milani, Lili, Almgren, Peter, Boutin, Thibaud, Debette, Stephanie, Ding, Jun, Giulianini, Franco, Holliday, Elizabeth G., Jackson, Anne U., Li-Gao, Ruifang, Lin, Wei-Yu, Luan, Jian'an, Mangino, Massimo, Oldmeadow, Christopher, Prins, Bram Peter, Qian, Yong, Sargurupremraj, Muralidharan, Shah, Nabi, Surendran, Praveen, Theriault, Sebastien, Verweij, Niek, Willems, Sara M., Zhao, Jing-Hua, Amouyel, Phillippe, Connell, John, de Mutsert, Renee, Doney, Alex S.F., Farrall, Martin, Menni, Cristina, Morris, Andrew D., Noordam, Raymond, Pare, Guillaume, Poulter, Neil R., Shields, Denis C., Stanton, Alice, Thom, Simon, Abecasis, Gonçalo, Amin, Najaf, Arking, Dan E., Ayers, Kristin L., Barbieri, Caterina M., Batini, Chiara, Bis, Joshua C., Blake, Tineka, Bochud, Murielle, Boehnke, Michael, Boerwinkle, Eric, Boomsma, Dorret I., Bottinger, Erwin P., Braund, Peter S., Brumat, Marco, Campbell, Archie, Campbell, Harry, Chakravarti, Aavinda, Chambers, John C., Chauhan, Ganesh, Ciullo, Marina, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J., Davies, Gail, de Borst, Martin H., de Geus, Eco J., Deary, Ian J., Deelen, Joris, Del Greco, M. Fabiola, Demirkale, Cumhur Yusuf, Dörr, Marcus, Ehret, Georg B., Elosua, Roberto, Enroth, Stefan, Erzurumluoglu, A. Mesut, Ferreira, Teresa, Franberg, Mattias, Franco, Oscar H., Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Goel, Anuj, Gow, Alan, Gudnason, Vilmundur, Guo, Xiuqing, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B., Harris, Sarah E., Hartman, Catharina A., Havulinna, Aki S., Hicks, Andrew A., Hofer, Edith, Hofman, Albert, Jottenga, Jouke-Jan, Huffman, Jennifer, Hwang, Shih-Jen, Ingelsson, Erik, James, Alan, Jansen, Rick, Jarvelin, Marjo-Riitta, Joehanes, Roby, Johansson, Asa, Johnson, Adnrew D., Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Keavney, Bernard D., Khaw, Kay-Tee, Knekt, Paul, Knight, Joanne, Kolcic, Ivana, Kooner, Jaspal S., Koskinen, Seppo, Kristiansson, Kati, Kutalik, Zoltan, Laan, Maris, Larson, Marty, Launer, Lenore J., Lehne, Benjamin, Lehtimäki, Terho, Liewald, David C.M., Lin, Li, Lind, Lars, Lindgren, Cecilia M., Liu, YongMei, Loos, Ruth J.F., Lopez, Lorna, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamasoula, Chrysovalanto, Marrugat, Jaume, Marten, Jonathan, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew, Morrison, Alanna C., Munson, Peter J., Nalls, Mike A., Nandakumar, Priyanka, Nelson, Christopher P., Niiranen, Teemu, Nolte, Ilja M., Nutile, Teresa, Oldehinkel, Albertine J., Oostra, Ben A., O'Reilly, Paul F., Org, Elin, Padmanabhan, Sandosh, Palmas, Walter, Palotie, Aarno, Pattie, Alison, Polasek, Ozren, Pramstaller, Peter P., Nguyen, Quang Tri, Raitakari, Olli T., Ren, Meixia, Rettig, Rainer, Rice, Kenneth, Ridker, Paul M., Ried, Janina S., Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rose, Lynda M., Rotter, Jerome I., Rudan, Igor, Ruggiero, Daniela, Saba, Yasaman, Sala, Cinzia F., Salomaa, Veikko, Samani, Nilesh J., Sarin, Antti-Pekka, Schmidt, Reinhold, Schmidt, Helena, Shrine, Nick, Siscovick, David, Smith, Albert V., Snieder, Harold, Sõber, Siim, Sorice, Rossella, Starr, John M., Stott, David, Strachan, David P., Strawbridge, Rona J., Sundström, Johan, Swertz, Morris A., Taylor, Kent D., Teumer, Alexander, Tobin, Martin D., Tomaszewski, Maciej, Toniolo, Daniela, Traglia, Michela, Trompet, Stella, Tuomilehto, Jaako, Tzourio, Christophe, Uitterlinden, Andre G., Vaez, Ahmad, van der Most, Peter J., van Duijn, Cornelia M., Vergnaud, Anne-Claire, verwoert, Germaine C., Vitart, Veronique, Völke, Uwe, Vollenweider, Peter, Vuckovic, Dragana, Watkins, Hugh, Wild, Sarah H., Willemsen, Gonneke, Wilson, James F., Wright, Alan F., Yao, Jie, Zemunik, Tatijana, Zhang, Weihua, Attia, John R., Butterworth, Adam S., Chasman, Daniel I., Conen, David, Cucca, Francesco, Danesh, John, Hayward, Caroline, Howson, Joanna M.M., Laakso, Markku, Lakatta, Edward G., Langenberg, Claudia, Melander, Olle, Mook-Kanamor, Dennis O., Palmer, Colin, Risch, Lorenz, Scott, Robert, Scott, Rodney, Sever, Peter, Spector, Tim D., van der Harst, Pim, Wareham, Nicholas J., Zeggini, Eleftheria, Levy, Daniel, Munroe, Patricia B., Newton-Cheh, Christopher, Brown, Morris J., Metspalu, Andres, Hung, Adriana M., O'Donnell, Christopher, Edwards, Todd L., Psaty, Bruce M., Tzoulaki, Ioanna, Barnes, Michael R., Wain, Louise V., Elliott, Paul, Caulfield, Mark J., Evangelou, Evangelos, Warren, Helen R., Mosen-Ansorena, David, Mifsud, Borbala, Pazoki, Raha, Gao, He, Ntritsos, Georgios, Dimou, Niki, Cabrera, Claudia, Karaman, Ibrahim, Ng, Fu Liang, Evangelou, Marina, Witkowska, Katarzyna, Tzanis, Evan, Hellwege, Jacklyn, Giri, Ayush, Edwards, Digna R. Velez, Sun, Yan V., Cho, Kelly, Gaziano, J. Michael, Wilson, Peter W.F., Tsao, Philip S., Kovesdy, Csaba P., Esko, Tonu, Magi, Reedik, Milani, Lili, Almgren, Peter, Boutin, Thibaud, Debette, Stephanie, Ding, Jun, Giulianini, Franco, Holliday, Elizabeth G., Jackson, Anne U., Li-Gao, Ruifang, Lin, Wei-Yu, Luan, Jian'an, Mangino, Massimo, Oldmeadow, Christopher, Prins, Bram Peter, Qian, Yong, Sargurupremraj, Muralidharan, Shah, Nabi, Surendran, Praveen, Theriault, Sebastien, Verweij, Niek, Willems, Sara M., Zhao, Jing-Hua, Amouyel, Phillippe, Connell, John, de Mutsert, Renee, Doney, Alex S.F., Farrall, Martin, Menni, Cristina, Morris, Andrew D., Noordam, Raymond, Pare, Guillaume, Poulter, Neil R., Shields, Denis C., Stanton, Alice, Thom, Simon, Abecasis, Gonçalo, Amin, Najaf, Arking, Dan E., Ayers, Kristin L., Barbieri, Caterina M., Batini, Chiara, Bis, Joshua C., Blake, Tineka, Bochud, Murielle, Boehnke, Michael, Boerwinkle, Eric, Boomsma, Dorret I., Bottinger, Erwin P., Braund, Peter S., Brumat, Marco, Campbell, Archie, Campbell, Harry, Chakravarti, Aavinda, Chambers, John C., Chauhan, Ganesh, Ciullo, Marina, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J., Davies, Gail, de Borst, Martin H., de Geus, Eco J., Deary, Ian J., Deelen, Joris, Del Greco, M. Fabiola, Demirkale, Cumhur Yusuf, Dörr, Marcus, Ehret, Georg B., Elosua, Roberto, Enroth, Stefan, Erzurumluoglu, A. Mesut, Ferreira, Teresa, Franberg, Mattias, Franco, Oscar H., Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Goel, Anuj, Gow, Alan, Gudnason, Vilmundur, Guo, Xiuqing, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B., Harris, Sarah E., Hartman, Catharina A., Havulinna, Aki S., Hicks, Andrew A., Hofer, Edith, Hofman, Albert, Jottenga, Jouke-Jan, Huffman, Jennifer, Hwang, Shih-Jen, Ingelsson, Erik, James, Alan, Jansen, Rick, Jarvelin, Marjo-Riitta, Joehanes, Roby, Johansson, Asa, Johnson, Adnrew D., Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Keavney, Bernard D., Khaw, Kay-Tee, Knekt, Paul, Knight, Joanne, Kolcic, Ivana, Kooner, Jaspal S., Koskinen, Seppo, Kristiansson, Kati, Kutalik, Zoltan, Laan, Maris, Larson, Marty, Launer, Lenore J., Lehne, Benjamin, Lehtimäki, Terho, Liewald, David C.M., Lin, Li, Lind, Lars, Lindgren, Cecilia M., Liu, YongMei, Loos, Ruth J.F., Lopez, Lorna, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamasoula, Chrysovalanto, Marrugat, Jaume, Marten, Jonathan, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew, Morrison, Alanna C., Munson, Peter J., Nalls, Mike A., Nandakumar, Priyanka, Nelson, Christopher P., Niiranen, Teemu, Nolte, Ilja M., Nutile, Teresa, Oldehinkel, Albertine J., Oostra, Ben A., O'Reilly, Paul F., Org, Elin, Padmanabhan, Sandosh, Palmas, Walter, Palotie, Aarno, Pattie, Alison, Polasek, Ozren, Pramstaller, Peter P., Nguyen, Quang Tri, Raitakari, Olli T., Ren, Meixia, Rettig, Rainer, Rice, Kenneth, Ridker, Paul M., Ried, Janina S., Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rose, Lynda M., Rotter, Jerome I., Rudan, Igor, Ruggiero, Daniela, Saba, Yasaman, Sala, Cinzia F., Salomaa, Veikko, Samani, Nilesh J., Sarin, Antti-Pekka, Schmidt, Reinhold, Schmidt, Helena, Shrine, Nick, Siscovick, David, Smith, Albert V., Snieder, Harold, Sõber, Siim, Sorice, Rossella, Starr, John M., Stott, David, Strachan, David P., Strawbridge, Rona J., Sundström, Johan, Swertz, Morris A., Taylor, Kent D., Teumer, Alexander, Tobin, Martin D., Tomaszewski, Maciej, Toniolo, Daniela, Traglia, Michela, Trompet, Stella, Tuomilehto, Jaako, Tzourio, Christophe, Uitterlinden, Andre G., Vaez, Ahmad, van der Most, Peter J., van Duijn, Cornelia M., Vergnaud, Anne-Claire, verwoert, Germaine C., Vitart, Veronique, Völke, Uwe, Vollenweider, Peter, Vuckovic, Dragana, Watkins, Hugh, Wild, Sarah H., Willemsen, Gonneke, Wilson, James F., Wright, Alan F., Yao, Jie, Zemunik, Tatijana, Zhang, Weihua, Attia, John R., Butterworth, Adam S., Chasman, Daniel I., Conen, David, Cucca, Francesco, Danesh, John, Hayward, Caroline, Howson, Joanna M.M., Laakso, Markku, Lakatta, Edward G., Langenberg, Claudia, Melander, Olle, Mook-Kanamor, Dennis O., Palmer, Colin, Risch, Lorenz, Scott, Robert, Scott, Rodney, Sever, Peter, Spector, Tim D., van der Harst, Pim, Wareham, Nicholas J., Zeggini, Eleftheria, Levy, Daniel, Munroe, Patricia B., Newton-Cheh, Christopher, Brown, Morris J., Metspalu, Andres, Hung, Adriana M., O'Donnell, Christopher, Edwards, Todd L., Psaty, Bruce M., Tzoulaki, Ioanna, Barnes, Michael R., Wain, Louise V., Elliott, Paul, and Caulfield, Mark J.

Abstract

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic, pulse pressure) to date in over one million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also reveal shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

Published
2018

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

Author

Wain, Louise V., Vaez, Ahmad, Jansen, Rick, Joehanes, Roby, van der Most, Peter J., Erzurumluoglu, A. Mesut, O'Reilly, Paul F., Cabrera, Claudia P., Warren, Helen R., 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., 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, Marten, Jonathan, Gandin, Ilaria, Harris, Sarah E., Zemunik, Tatijana, Lu, Yingchang, Evangelou, Evangelos, 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., Barnes, Michael R., Batini, Chiara, Beilby, John, Blake, Tineka, Boehnke, Michael, Bottinger, Erwin P., Braund, Peter S., Brown, Morris, Brumat, Marco, Campbell, Harry, Chambers, John C., Cocca, Massimiliano, Collins, Francis, Connell, John, 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, Farrall, Martin, Ferreira, Teresa, Franberg, Mattias, Gao, He, Giedraitis, Vilmantas, Gieger, Christian, Giulianini, Franco, Gow, Alan J., Hamsten, Anders, Harris, Tamara B., Hofman, Albert, Holliday, Elizabeth G., Hui, Jennie, Jarvelin, Marjo-Riitta, Johansson, Åsa, 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, Lars, Mach, Francois, Mamasoula, Chrysovalanto, Menni, Cristina, Mifsud, Borbala, 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, Padmanabhan, Sandosh, Palotie, Aarno, Pare, Guillaume, Pattie, Alison, Penninx, Brenda W. J. H., Poulter, Neil, Pramstaller, Peter P., Raitakari, Olli T., Ren, Meixia, 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., Shields, Denis C., Siscovick, David, Sorice, Rossella, Stanton, Alice, Stott, David J., Sundström, Johan, Swertz, Morris, Taylor, Kent D., Thom, Simon, Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre G., Volker, Uwe, Vollenweider, Peter, Wild, Sarah, Willemsen, Gonneke, Wright, Alan F., Yao, Jie, Theriault, Sebastien, Conen, David, Attia, John, Sever, Peter, Debette, Stephanie, Mook-Kanamori, Dennis O., Zeggini, Eleftheria, Spector, Tim D., van der Harst, Pim, Palmer, Colin N. A., Vergnaud, Anne-Claire, Loos, Ruth J. F., Polasek, Ozren, Starr, John M., Girotto, Giorgia, Hayward, Caroline, Kooner, Jaspal S., Lindgren, Cecila M., Vitart, Veronique, Samani, Nilesh J., 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, Maris, Liu, YongMei, Watkins, Hugh, Hartman, Catharina A., Salomaa, Veikko, Toniolo, Daniela, Perola, Markus, 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, Metspalu, Andres, Ingelsson, Erik, Boomsma, Dorret I., Franco, Oscar H., Bochud, Murielle, Newton-Cheh, Christopher, Munroe, Patricia B., Elliott, Paul, Chasman, Daniel I., Chakravarti, Aravinda, Knight, Joanne, Morris, Andrew P., Levy, Daniel, Tobin, Martin D., Snieder, Harold, Caulfield, Mark J., Ehret, Georg B., Alistair, T. Y., Betholdson, J. -P, Xiao, Limin, Wain, Louise V., Vaez, Ahmad, Jansen, Rick, Joehanes, Roby, van der Most, Peter J., Erzurumluoglu, A. Mesut, O'Reilly, Paul F., Cabrera, Claudia P., Warren, Helen R., 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., 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, Marten, Jonathan, Gandin, Ilaria, Harris, Sarah E., Zemunik, Tatijana, Lu, Yingchang, Evangelou, Evangelos, 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., Barnes, Michael R., Batini, Chiara, Beilby, John, Blake, Tineka, Boehnke, Michael, Bottinger, Erwin P., Braund, Peter S., Brown, Morris, Brumat, Marco, Campbell, Harry, Chambers, John C., Cocca, Massimiliano, Collins, Francis, Connell, John, 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, Farrall, Martin, Ferreira, Teresa, Franberg, Mattias, Gao, He, Giedraitis, Vilmantas, Gieger, Christian, Giulianini, Franco, Gow, Alan J., Hamsten, Anders, Harris, Tamara B., Hofman, Albert, Holliday, Elizabeth G., Hui, Jennie, Jarvelin, Marjo-Riitta, Johansson, Åsa, 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, Lars, Mach, Francois, Mamasoula, Chrysovalanto, Menni, Cristina, Mifsud, Borbala, 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, Padmanabhan, Sandosh, Palotie, Aarno, Pare, Guillaume, Pattie, Alison, Penninx, Brenda W. J. H., Poulter, Neil, Pramstaller, Peter P., Raitakari, Olli T., Ren, Meixia, 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., Shields, Denis C., Siscovick, David, Sorice, Rossella, Stanton, Alice, Stott, David J., Sundström, Johan, Swertz, Morris, Taylor, Kent D., Thom, Simon, Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, Andre G., Volker, Uwe, Vollenweider, Peter, Wild, Sarah, Willemsen, Gonneke, Wright, Alan F., Yao, Jie, Theriault, Sebastien, Conen, David, Attia, John, Sever, Peter, Debette, Stephanie, Mook-Kanamori, Dennis O., Zeggini, Eleftheria, Spector, Tim D., van der Harst, Pim, Palmer, Colin N. A., Vergnaud, Anne-Claire, Loos, Ruth J. F., Polasek, Ozren, Starr, John M., Girotto, Giorgia, Hayward, Caroline, Kooner, Jaspal S., Lindgren, Cecila M., Vitart, Veronique, Samani, Nilesh J., 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, Maris, Liu, YongMei, Watkins, Hugh, Hartman, Catharina A., Salomaa, Veikko, Toniolo, Daniela, Perola, Markus, 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, Metspalu, Andres, Ingelsson, Erik, Boomsma, Dorret I., Franco, Oscar H., Bochud, Murielle, Newton-Cheh, Christopher, Munroe, Patricia B., Elliott, Paul, Chasman, Daniel I., Chakravarti, Aravinda, Knight, Joanne, Morris, Andrew P., Levy, Daniel, Tobin, Martin D., Snieder, Harold, Caulfield, Mark J., Ehret, Georg B., Alistair, T. Y., Betholdson, J. -P, and Xiao, Limin

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.

Published
2017
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38. 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, 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, 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, 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., Brumat, Marco, Campbell, 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, Harris, Tamara B., Hofman, Albert, Holliday, Elizabeth G., Jarvelin, Marjo-Riitta, Johansson, Åsa, 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, Lars, Mach, Francois, 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, 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., Sundström, Johan, Swertz, Morris, 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, Maris, Liu, YongMei, Watkins, Hugh, Hartman, Catharina A., Salomaa, Veikko, Toniolo, Daniela, Perola, Markus, 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., 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, 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, 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., Brumat, Marco, Campbell, 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, Harris, Tamara B., Hofman, Albert, Holliday, Elizabeth G., Jarvelin, Marjo-Riitta, Johansson, Åsa, 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, Lars, Mach, Francois, 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, 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., Sundström, Johan, Swertz, Morris, 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, Maris, Liu, YongMei, Watkins, Hugh, Hartman, Catharina A., Salomaa, Veikko, Toniolo, Daniela, Perola, Markus, 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, and Morris, Andrew P.

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
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39. Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Author

Christophersen, Ingrid E., Rienstra, Michiel, Roselli, Carolina, Yin, Xiaoyan, Geelhoed, Bastiaan, Barnard, John, Lin, Honghuang, Arking, Dan E., Smith, Albert V., Albert, Christine M., Chaffin, Mark, Tucker, Nathan R., Li, Molong, Klarin, Derek, Bihlmeyer, Nathan A., Low, Siew-Kee, Weeke, Peter E., Mueller-Nurasyid, Martina, Smith, J. Gustav, Brody, Jennifer A., Niemeijer, Maartje N., Doerr, Marcus, Trompet, Stella, Huffman, Jennifer, Gustafsson, Stefan, Schurmann, Claudia, Kleber, Marcus E., Lyytikainen, Leo-Pekka, Seppala, Ilkka, Malik, Rainer, Horimoto, Andrea R. V. R., Perez, Marco, Sinisalo, Juha, Aeschbacher, Stefanie, Theriault, Sebastien, Yao, Jie, Radmanesh, Farid, Weiss, Stefan, Teumer, Alexander, Choi, Seung Hoan, Weng, Lu-Chen, Clauss, Sebastian, Deo, Rajat, Rader, Daniel J., Shah, Svati H., Sun, Albert, Hopewell, Jemma C., Debette, Stephanie, Chauhan, Ganesh, Yang, Qiong, Worrall, Bradford B., Pare, Guillaume, Kamatani, Yoichiro, Hagemeijer, Yanick P., Verweij, Niek, Siland, Joylene E., Kubo, Michiaki, Smith, Jonathan D., Van Wagoner, David R., Bis, Joshua C., Perz, Siegfried, Psaty, Bruce M., Ridker, Paul M., Magnani, Jared W., Harris, Tamara B., Launer, Lenore J., Shoemaker, M. Benjamin, Padmanabhan, Sandosh, Haessler, Jeffrey, Bartz, Traci M., Waldenberger, Melanie, Lichtner, Peter, Arendt, Marina, Krieger, Jose E., Kahonen, Mika, Risch, Lorenz, Mansur, Alfredo J., Peters, Annette, Smith, Blair H., Lind, Lars, Scott, Stuart A., Lu, Yingchang, Bottinger, Erwin B., Hernesniemi, Jussi, Lindgren, Cecilia M., Wong, Jorge A., Huang, Jie, Eskola, Markku, Morris, Andrew P., Ford, Ian, Reiner, Alex P., Delgado, Graciela, Chen, Lin Y., Chen, Yii-Der Ida, Sandhu, Roopinder K., Li, Man, Boerwinkle, Eric, Eisele, Lewin, Lannfelt, Lars, Rost, Natalia, Anderson, Christopher D., Taylor, Kent D., Campbell, Archie, Magnusson, Patrik K., Porteous, David, Hocking, Lynne J., Vlachopoulou, Efthymia, Pedersen, Nancy L., Nikus, Kjell, Orho-Melander, Marju, Hamsten, Anders, Heeringa, Jan, Denny, Joshua C., Kriebel, Jennifer, Darbar, Dawood, Newton-Cheh, Christopher, Shaffer, Christian, Macfarlane, Peter W., Heilmann-Heimbach, Stefanie, Almgren, Peter, Huang, Paul L., Sotoodehnia, Nona, Soliman, Elsayed Z., Uitterlinden, Andre G., Hofman, Albert, Franco, Oscar H., Voelker, Uwe, Joeckel, Karl-Heinz, Sinner, Moritz F., Lin, Henry J., Guo, Xiuqing, Dichgans, Martin, Ingelsson, Erik, Kooperberg, Charles, Melander, Olle, Loos, Ruth J. F., Laurikka, Jari, Conen, David, Rosand, Jonathan, van der Harst, Pim, Lokki, Marja-Liisa, Kathiresan, Sekar, Pereira, Alexandre, Jukema, J. Wouter, Hayward, Caroline, Rotter, Jerome I., Maerz, Winfried, Lehtimaki, Terho, Stricker, Bruno H., Chung, Mina K., Felix, Stephan B., Gudnason, Vilmundur, Alonso, Alvaro, Roden, Dan M., Kaeaeb, Stefan, Chasman, Daniel I., Heckbert, Susan R., Benjamin, Emelia J., Tanaka, Toshihiro, Lunetta, Kathryn L., Lubitz, Steven A., Ellinor, Patrick T., Christophersen, Ingrid E., Rienstra, Michiel, Roselli, Carolina, Yin, Xiaoyan, Geelhoed, Bastiaan, Barnard, John, Lin, Honghuang, Arking, Dan E., Smith, Albert V., Albert, Christine M., Chaffin, Mark, Tucker, Nathan R., Li, Molong, Klarin, Derek, Bihlmeyer, Nathan A., Low, Siew-Kee, Weeke, Peter E., Mueller-Nurasyid, Martina, Smith, J. Gustav, Brody, Jennifer A., Niemeijer, Maartje N., Doerr, Marcus, Trompet, Stella, Huffman, Jennifer, Gustafsson, Stefan, Schurmann, Claudia, Kleber, Marcus E., Lyytikainen, Leo-Pekka, Seppala, Ilkka, Malik, Rainer, Horimoto, Andrea R. V. R., Perez, Marco, Sinisalo, Juha, Aeschbacher, Stefanie, Theriault, Sebastien, Yao, Jie, Radmanesh, Farid, Weiss, Stefan, Teumer, Alexander, Choi, Seung Hoan, Weng, Lu-Chen, Clauss, Sebastian, Deo, Rajat, Rader, Daniel J., Shah, Svati H., Sun, Albert, Hopewell, Jemma C., Debette, Stephanie, Chauhan, Ganesh, Yang, Qiong, Worrall, Bradford B., Pare, Guillaume, Kamatani, Yoichiro, Hagemeijer, Yanick P., Verweij, Niek, Siland, Joylene E., Kubo, Michiaki, Smith, Jonathan D., Van Wagoner, David R., Bis, Joshua C., Perz, Siegfried, Psaty, Bruce M., Ridker, Paul M., Magnani, Jared W., Harris, Tamara B., Launer, Lenore J., Shoemaker, M. Benjamin, Padmanabhan, Sandosh, Haessler, Jeffrey, Bartz, Traci M., Waldenberger, Melanie, Lichtner, Peter, Arendt, Marina, Krieger, Jose E., Kahonen, Mika, Risch, Lorenz, Mansur, Alfredo J., Peters, Annette, Smith, Blair H., Lind, Lars, Scott, Stuart A., Lu, Yingchang, Bottinger, Erwin B., Hernesniemi, Jussi, Lindgren, Cecilia M., Wong, Jorge A., Huang, Jie, Eskola, Markku, Morris, Andrew P., Ford, Ian, Reiner, Alex P., Delgado, Graciela, Chen, Lin Y., Chen, Yii-Der Ida, Sandhu, Roopinder K., Li, Man, Boerwinkle, Eric, Eisele, Lewin, Lannfelt, Lars, Rost, Natalia, Anderson, Christopher D., Taylor, Kent D., Campbell, Archie, Magnusson, Patrik K., Porteous, David, Hocking, Lynne J., Vlachopoulou, Efthymia, Pedersen, Nancy L., Nikus, Kjell, Orho-Melander, Marju, Hamsten, Anders, Heeringa, Jan, Denny, Joshua C., Kriebel, Jennifer, Darbar, Dawood, Newton-Cheh, Christopher, Shaffer, Christian, Macfarlane, Peter W., Heilmann-Heimbach, Stefanie, Almgren, Peter, Huang, Paul L., Sotoodehnia, Nona, Soliman, Elsayed Z., Uitterlinden, Andre G., Hofman, Albert, Franco, Oscar H., Voelker, Uwe, Joeckel, Karl-Heinz, Sinner, Moritz F., Lin, Henry J., Guo, Xiuqing, Dichgans, Martin, Ingelsson, Erik, Kooperberg, Charles, Melander, Olle, Loos, Ruth J. F., Laurikka, Jari, Conen, David, Rosand, Jonathan, van der Harst, Pim, Lokki, Marja-Liisa, Kathiresan, Sekar, Pereira, Alexandre, Jukema, J. Wouter, Hayward, Caroline, Rotter, Jerome I., Maerz, Winfried, Lehtimaki, Terho, Stricker, Bruno H., Chung, Mina K., Felix, Stephan B., Gudnason, Vilmundur, Alonso, Alvaro, Roden, Dan M., Kaeaeb, Stefan, Chasman, Daniel I., Heckbert, Susan R., Benjamin, Emelia J., Tanaka, Toshihiro, Lunetta, Kathryn L., Lubitz, Steven A., and Ellinor, Patrick T.

Abstract

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death(1,2). Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups(3-7). To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery(8).

Published
2017
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41. Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium

Author

Weng, Lu-Chen, Lunetta, Kathryn L., Müller-Nurasyid, Martina, Smith, Albert Vernon, Thériault, Sébastien, Weeke, Peter E., Barnard, John, Bis, Joshua C., Lyytikäinen, Leo-Pekka, Kleber, Marcus E., Martinsson, Andreas, Lin, Henry J., Rienstra, Michiel, Trompet, Stella, Krijthe, Bouwe P., Dörr, Marcus, Klarin, Derek, Chasman, Daniel I., Sinner, Moritz F., Waldenberger, Melanie, Launer, Lenore J., Harris, Tamara B., Soliman, Elsayed Z., Alonso, Alvaro, Paré, Guillaume, Teixeira, Pedro L., Denny, Joshua C., Shoemaker, M. Benjamin, Van Wagoner, David R., Smith, Jonathan D., Psaty, Bruce M., Sotoodehnia, Nona, Taylor, Kent D., Kähönen, Mika, Nikus, Kjell, Delgado, Graciela E., Melander, Olle, Engström, Gunnar, Yao, Jie, Guo, Xiuqing, Christophersen, Ingrid E., Ellinor, Patrick T., Geelhoed, Bastiaan, Verweij, Niek, Macfarlane, Peter, Ford, Ian, Heeringa, Jan, Franco, Oscar H., Uitterlinden, André G., Völker, Uwe, Teumer, Alexander, Rose, Lynda M., Kääb, Stefan, Gudnason, Vilmundur, Arking, Dan E., Conen, David, Roden, Dan M., Chung, Mina K., Heckbert, Susan R., Benjamin, Emelia J., Lehtimäki, Terho, März, Winfried, Smith, J. Gustav, Rotter, Jerome I., van der Harst, Pim, Jukema, J. Wouter, Stricker, Bruno H., Felix, Stephan B., Albert, Christine M., and Lubitz, Steven A.

Abstract

It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent studies (131,441 individuals, including 5,722 with AF). In the discovery analysis, the AF risk associated with the minor rs6817105 allele (at the PITX2 locus) was greater among subjects ≤ 65 years of age than among those > 65 years (interaction p-value = 4.0 × 10−5). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value = 1.7 × 10−8). We observed one genome-wide significant interaction with body mass index and several suggestive interactions with age, sex, and body mass index in the discovery analysis. However, none was replicated in the independent sample. Our findings suggest that the pathogenesis of AF may differ according to age in individuals of European descent, but we did not observe evidence of statistically significant genetic interactions with sex, body mass index, or hypertension on AF risk.

Published
2017
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43. Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation (vol 49, pg 946, 2017)

Author

Christophersen, Ingrid E., Rienstra, Michiel, Roselli, Carolina, Yin, Xiaoyan, Geelhoed, Bastiaan, Barnard, John, Lin, Honghuang, Arking, Dan E., Smith, Albert V., Albert, Christine M., Chaffin, Mark, Tucker, Nathan R., Li, Molong, Klarin, Derek, Bihlmeyer, Nathan A., Low, Siew-Kee, Weeke, Peter E., Muller-Nurasyid, Martina, Smith, J. Gustav, Brody, Jennifer A., Niemeijer, Maartje N., Dorr, Marcus, Trompet, Stella, Huffman, Jennifer, Gustafsson, Stefan, Schurmann, Claudia, Kleber, Marcus E., Lyytikainen, Leo-Pekka, Seppala, Ilkka, Malik, Rainer, Horimoto, Andrea R. V. R., Perez, Marco, Sinisalo, Juha, Aeschbacher, Stefanie, Theriault, Sebastien, Yao, Jie, Radmanesh, Farid, Weiss, Stefan, Teumer, Alexander, Choi, Seung Hoan, Weng, Lu-Chen, Clauss, Sebastian, Deo, Rajat, Rader, Daniel J., Shah, Svati H., Sun, Albert, Hopewell, Jemma C., Debette, Stephanie, Chauhan, Ganesh, Yang, Qiong, Worrall, Bradford B., Pare, Guillaume, Kamatani, Yoichiro, Hagemeijer, Yanick P., Verweij, Niek, Siland, Joylene E., Kubo, Michiaki, Smith, Jonathan D., Wagoner, David R., Bis, Joshua C., Perz, Siegfried, Psaty, Bruce M., Ridker, Paul M., Magnani, Jared W., Harris, Tamara B., Launer, Lenore J., Shoemaker, M. Benjamin, Padmanabhan, Sandosh, Haessler, Jeffrey, Bartz, Traci M., Waldenberger, Melanie, Lichtner, Peter, Arendt, Marina, Krieger, Jose E., Kahonen, Mika, Risch, Lorenz, Mansur, Alfredo J., Peters, Annette, Smith, Blair H., Lind, Lars, Scott, Stuart A., Lu, Yingchang, Bottinger, Erwin B., Hernesniemi, Jussi, Lindgren, Cecilia M., Wong, Jorge A., Huang, Jie, Eskola, Markku, Morris, Andrew P., Ford, Ian, Reiner, Alex P., Delgado, Graciela, Chen, Lin Y., Chen, Yii-Der Ida, Sandhu, Roopinder K., Li, Man, Boerwinkle, Eric, Eisele, Lewin, Lannfelt, Lars, Rost, Natalia, Anderson, Christopher D., Taylor, Kent D., Campbell, Archie, Magnusson, Patrik K., Porteous, David, Hocking, Lynne J., Vlachopoulou, Efthymia, Pedersen, Nancy L., Nikus, Kjell, Orho-Melander, Marju, Hamsten, Anders, Heeringa, Jan, Denny, Joshua C., Kriebel, Jennifer, Darbar, Dawood, Newton-Cheh, Christopher, Shaffer, Christian, Macfarlane, Peter W., Stefanie Heilmann-Heimbach, Almgren, Peter, Huang, Paul L., Sotoodehnia, Nona, Soliman, Elsayed Z., Uitterlinden, Andre G., Hofman, Albert, Franco, Oscar H., Volker, Uwe, Jockel, Karl-Heinz, Sinner, Moritz F., Lin, Henry J., Guo, Xiuqing, Dichgans, Martin, Ingelsson, Erik, Kooperberg, Charles, Melander, Olle, Loos, Ruth J. F., Laurikka, Jari, Conen, David, Rosand, Jonathan, Harst, Pim, Lokki, Marja-Liisa, Kathiresan, Sekar, Pereira, Alexandre, Jukema, J. Wouter, Hayward, Caroline, Rotter, Jerome I., Marz, Winfried, Lehtimaki, Terho, Stricker, Bruno H., Chung, Mina K., Felix, Stephan B., Gudnason, Vilmundur, Alonso, Alvaro, Roden, Dan M., Kaab, Stefan, Chasman, Daniel I., Heckbert, Susan R., Benjamin, Emelia J., Tanaka, Toshihiro, Lunetta, Kathryn L., Lubitz, Steven A., Ellinor, Patrick T., Metastroke Isgc, Consortium, Charge, Neurology Working Group Con, and AFGen Consortium

44. Abstract 14462: Long-Term Exposure to Elevated Lipoprotein(a) Levels Influences Human Longevity

Author

Arsenault, Benoit, Pelletier, William, Kaiser, Yannick, Perrot, Nicolas, Couture, Christian, Khaw, Kay-Tee, Wareham, Nicholas, Bosse, Yohan, Pibarot, Philippe, Stroes, Erik S, Mathieu, Patrick, Theriault, Sebastien, and Boekholdt, S. Matthijs

Abstract

Background:Elevated Lipoprotein(a) (Lp[a]) levels are associated with a broad range of atherosclerotic cardiovascular diseases. The impact of high Lp(a) levels on human longevity is however controversial. Our objectives were to determine whether genetically-determined Lp(a) levels are associated with parental lifespan and healthspan and to assess the association between Lp(a) levels and long-term all-cause and cardiovascular mortality.Methods:We determined the association between 26 independent single nucleotide polymorphisms (SNPs) at the LPAlocus weighted for their effect on Lp(a) levels on parental lifespan using 139,362 participants from the UK Biobank, as well as with summary statistics of a genome-wide association study (GWAS) of over one million lifespans (UK Biobank and LifeGen consortium). The association between Lp(a) levels and all-cause and cardiovascular mortality in 18,720 participants from the EPIC-Norfolk study was also investigated.Results:In the UK Biobank, increases in the wGRS (weighted for a 50 mg/dL increase in Lp(a) levels) were inversely associated with a high parental lifespan (odds ratio=0.92, 95% confidence interval [CI]=0.89-0.94, p=2.7x10-8). Using Egger Mendelian randomixation (Egger-MR), we found a negative association between the effect of LPA SNPs and parental lifespan (Egger-MR slope = -0.0019 [0.0002], p=2.22x10-18). During the 20-year follow-up of the EPIC-Norfolk study, 5686 participants died (2412 from CVD-related causes). Compared to individuals with Lp(a) levels below the 50thpercentile of the Lp(a) distribution, those with Lp(a) levels equal or above the 95thpercentile of the population distribution (?70 mg/dL) had HRs of 1.22 (95% CI=1.09-1.37, event rate 37.5%) and 1.71 (95% CI=1.46-2.00), for all-cause mortality and cardiovascular mortality, respectively.Conclusions:Results of this study suggest a potentially causal effect of Lp(a) on human longevity, support the use of parental lifespan as a tool to study the genetic determinants of human longevity, and provide a rationale for trials of Lp(a)-lowering therapy in individuals with high Lp(a) levels.

Published
2019
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45. 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

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