The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Georg B. Ehret, Teresa Ferreira, Daniel I. Chasman, Anne U. Jackson, Ellen M. Schmidt, Toby Johnson, Gudmar Thorleifsson, Jian'An Luan, Louise A. Donnelly, Stavroula Kanoni, Ann Kristin Petersen, Vasyl Pihur, Rona J. Strawbridge, Dmitry Shungin, Maria F. Hughes, Osorio Meirelles, Marika Kaakinen, Nabila Bouatia-Naji, Kati Kristiansson, Sonia Shah & 293 others Marcus E. Kleber, Xiuqing Guo, Leo Pekka Lyytikäinen, Cristiano Fava, Niclas Eriksson, Ilja M. Nolte, Patrik K. Magnusson, Elias L. Salfati, Loukianos S. Rallidis, Elizabeth Theusch, Andrew J.P. Smith, Lasse Folkersen, Kate Witkowska, Tune H. Pers, Roby Joehanes, Stuart K. Kim, Lazaros Lataniotis, Rick Jansen, Andrew D. Johnson, Helen Warren, Young Jin Kim, Wei Zhao, Ying Wu, Bamidele O. Tayo, Murielle Bochud, Devin Absher, Linda S. Adair, Najaf Amin, Dan E. Arking, Tomas Axelsson, Damiano Baldassarre, Beverley Balkau, Stefania Bandinelli, Michael R. Barnes, Inês Barroso, Stephen Bevan, Joshua C. Bis, Gyda Bjornsdottir, Michael Boehnke, Eric Boerwinkle, Lori L. Bonnycastle, Dorret I. Boomsma, Stefan R. Bornstein, Morris J. Brown, Michel Burnier, Claudia P. Cabrera, John C. Chambers, I. Shou Chang, Ching Yu Cheng, Peter S. Chines, Ren Hua Chung, Francis S. Collins, John M. Connell, Angela Döring, Jean Dallongeville, John Danesh, Ulf De Faire, Graciela Delgado, Anna F. Dominiczak, Alex S.F. Doney, Fotios Drenos, Sarah Edkins, John D. Eicher, Roberto Elosua, Stefan Enroth, Jeanette Erdmann, Per Eriksson, Tonu Esko, Evangelos Evangelou, Alun Evans, Tove Fall, Martin Farrall, Janine F. Felix, Jean Ferrières, Luigi Ferrucci, Myriam Fornage, Terrence Forrester, Nora Franceschini, Oscar H. Franco, Anders Franco-Cereceda, Ross M. Fraser, Santhi K. Ganesh, He Gao, Karl Gertow, Francesco Gianfagna, Bruna Gigante, Franco Giulianini, Anuj Goel, Alison H. Goodall, Mark O. Goodarzi, Mathias Gorski, Jürgen Gräßler, Christopher J. Groves, Vilmundur Gudnason, Ulf Gyllensten, Göran Hallmans, Anna Liisa Hartikainen, Maija Hassinen, Aki S. Havulinna, Caroline Hayward, Serge Hercberg, Karl Heinz Herzig, Andrew A. Hicks, Aroon D. Hingorani, Joel N. Hirschhorn, Albert Hofman, Jostein Holmen, Oddgeir Lingaas Holmen, Jouke Jan Hottenga, Phil Howard, Chao A. Hsiung, Steven Hunt, M. Arfan Ikram, Thomas Illig, Carlos Iribarren, Richard A. Jensen, Mika Kähönen, Hyun Min Kang, Sekar Kathiresan, Brendan J. Keating, Kay Tee Khaw, Yun Kyoung Kim, Eric Kim, Mika Kivimaki, Norman Klopp, Genovefa Kolovou, Pirjo Komulainen, Jaspal S. Kooner, Gulum Kosova, Ronald M. Krauss, Diana Kuh, Zoltan Kutalik, Johanna Kuusisto, Kirsti Kvaløy, Timo A. Lakka, Nanette R. Lee, I. Te Lee, Wen Jane Lee, Daniel Levy, Xiaohui Li, Kae Woei Liang, Honghuang Lin, Li Lin, Jaana Lindström, Stéphane Lobbens, Satu Männistö, Gabriele Müller, Martina Müller-Nurasyid, François Mach, Hugh S. Markus, Eirini Marouli, Mark I. McCarthy, Colin A. McKenzie, Pierre Meneton, Cristina Menni, Andres Metspalu, Vladan Mijatovic, Leena Moilanen, May E. Montasser, Andrew D. Morris, Alanna C. Morrison, Antonella Mulas, Ramaiah Nagaraja, Narisu Narisu, Kjell Nikus, Christopher J. O'Donnell, Paul F. O'Reilly, Ken K. Ong, Fred Paccaud, Cameron D. Palmer, Afshin Parsa, Nancy L. Pedersen, Brenda W. Penninx, Markus Perola, Annette Peters, Neil Poulter, Peter P. Pramstaller, Bruce M. Psaty, Thomas Quertermous, Dabeeru C. Rao, Asif Rasheed, N. William Rayner, Frida Renström, Rainer Rettig, Kenneth M. Rice, Robert Roberts, Lynda M. Rose, Jacques Rossouw, Nilesh J. Samani, Serena Sanna, Jouko Saramies, Heribert Schunkert, Sylvain Sebert, Wayne H.H. Sheu, Young Ah Shin, Xueling Sim, Johannes H. Smit, Albert V. Smith, Maria X. Sosa, Tim D. Spector, Alena Stančáková, Alice V. Stanton, Kathleen E. Stirrups, Heather M. Stringham, Johan Sundstrom, Amy J. Swift, Ann Christine Syvänen, E. Shyong Tai, Toshiko Tanaka, Kirill V. Tarasov, Alexander Teumer, Unnur Thorsteinsdottir, Martin D. Tobin, Elena Tremoli, Andre G. Uitterlinden, Matti Uusitupa, Ahmad Vaez, Dhananjay Vaidya, Cornelia M. Van Duijn, Erik P.A. Van Iperen, Ramachandran S. Vasan, Germaine C. Verwoert, Jarmo Virtamo, Veronique Vitart, Benjamin F. Voight, Peter Vollenweider, Aline Wagner, Louise V. Wain, Nicholas J. Wareham, Hugh Watkins, Alan B. Weder, Harm Jan Westra, Rainford Wilks, Tom Wilsgaard, James F. Wilson, Tien Y. Wong, Tsun Po Yang, Jie Yao, Loic Yengo, Weihua Zhang, Jing Hua Zhao, Xiaofeng Zhu, Pascal Bovet, Richard S. Cooper, Karen L. Mohlke, Danish Saleheen, Jong Young Lee, Paul Elliott, Hinco J. Gierman, Cristen J. Willer, Lude Franke, G. Kees Hovingh, Kent D. Taylor, George Dedoussis, Peter Sever, Andrew Wong, Lars Lind, Themistocles L. Assimes, Inger Njølstad, Peter E.H. Schwarz, Claudia Langenberg, Harold Snieder, Mark J. Caulfield, Olle Melander, Markku Laakso, Juha Saltevo, Rainer Rauramaa, Jaakko Tuomilehto, Erik Ingelsson, Terho Lehtimäki, Kristian Hveem, Walter Palmas, Winfried März, Meena Kumari, Veikko Salomaa, Yii Der I. Chen, Jerome I. Rotter, Philippe Froguel, Marjo Riitta Jarvelin, Edward G. Lakatta, Kari Kuulasmaa, Paul W. Franks, Anders Hamsten, H. Erich Wichmann, Colin N.A. Palmer, Kari Stefansson, Paul M. Ridker, Ruth J.F. Loos, Aravinda Chakravarti, Panos Deloukas, Andrew P. Morris, Christopher Newton-Cheh, Patricia B. Munroe

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

Original languageEnglish
Pages (from-to)1171-1184
Number of pages14
JournalNature Genetics
Volume48
Issue number10
DOIs
Publication statusPublished - 1 Oct 2016

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Blood Pressure
Single Nucleotide Polymorphism
Kidney
Blood Vessels
Endothelial Cells
Genotype
Genome

ASJC Scopus subject areas

  • Genetics

Cite this

Ehret, G. B., Ferreira, T., Chasman, D. I., Jackson, A. U., Schmidt, E. M., Johnson, T., ... Munroe, P. B. (2016). The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nature Genetics, 48(10), 1171-1184. https://doi.org/10.1038/ng.3667

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. / Ehret, Georg B.; Ferreira, Teresa; Chasman, Daniel I.; Jackson, Anne U.; Schmidt, Ellen M.; Johnson, Toby; Thorleifsson, Gudmar; Luan, Jian'An; Donnelly, Louise A.; Kanoni, Stavroula; Petersen, Ann Kristin; Pihur, Vasyl; Strawbridge, Rona J.; Shungin, Dmitry; Hughes, Maria F.; Meirelles, Osorio; Kaakinen, Marika; Bouatia-Naji, Nabila; Kristiansson, Kati; Shah, Sonia; Kleber, Marcus E.; Guo, Xiuqing; Lyytikäinen, Leo Pekka; Fava, Cristiano; Eriksson, Niclas; Nolte, Ilja M.; Magnusson, Patrik K.; Salfati, Elias L.; Rallidis, Loukianos S.; Theusch, Elizabeth; Smith, Andrew J.P.; Folkersen, Lasse; Witkowska, Kate; Pers, Tune H.; Joehanes, Roby; Kim, Stuart K.; Lataniotis, Lazaros; Jansen, Rick; Johnson, Andrew D.; Warren, Helen; Kim, Young Jin; Zhao, Wei; Wu, Ying; Tayo, Bamidele O.; Bochud, Murielle; Absher, Devin; Adair, Linda S.; Amin, Najaf; Arking, Dan E.; Axelsson, Tomas; Baldassarre, Damiano; Balkau, Beverley; Bandinelli, Stefania; Barnes, Michael R.; Barroso, Inês; Bevan, Stephen; Bis, Joshua C.; Bjornsdottir, Gyda; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L.; Boomsma, Dorret I.; Bornstein, Stefan R.; Brown, Morris J.; Burnier, Michel; Cabrera, Claudia P.; Chambers, John C.; Chang, I. Shou; Cheng, Ching Yu; Chines, Peter S.; Chung, Ren Hua; Collins, Francis S.; Connell, John M.; Döring, Angela; Dallongeville, Jean; Danesh, John; De Faire, Ulf; Delgado, Graciela; Dominiczak, Anna F.; Doney, Alex S.F.; Drenos, Fotios; Edkins, Sarah; Eicher, John D.; Elosua, Roberto; Enroth, Stefan; Erdmann, Jeanette; Eriksson, Per; Esko, Tonu; Evangelou, Evangelos; Evans, Alun; Fall, Tove; Farrall, Martin; Felix, Janine F.; Ferrières, Jean; Ferrucci, Luigi; Fornage, Myriam; Forrester, Terrence; Franceschini, Nora; Franco, Oscar H.; Franco-Cereceda, Anders; Fraser, Ross M.; Ganesh, Santhi K.; Gao, He; Gertow, Karl; Gianfagna, Francesco; Gigante, Bruna; Giulianini, Franco; Goel, Anuj; Goodall, Alison H.; Goodarzi, Mark O.; Gorski, Mathias; Gräßler, Jürgen; Groves, Christopher J.; Gudnason, Vilmundur; Gyllensten, Ulf; Hallmans, Göran; Hartikainen, Anna Liisa; Hassinen, Maija; Havulinna, Aki S.; Hayward, Caroline; Hercberg, Serge; Herzig, Karl Heinz; Hicks, Andrew A.; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofman, Albert; Holmen, Jostein; Holmen, Oddgeir Lingaas; Hottenga, Jouke Jan; Howard, Phil; Hsiung, Chao A.; Hunt, Steven; Ikram, M. Arfan; Illig, Thomas; Iribarren, Carlos; Jensen, Richard A.; Kähönen, Mika; Kang, Hyun Min; Kathiresan, Sekar; Keating, Brendan J.; Khaw, Kay Tee; Kim, Yun Kyoung; Kim, Eric; Kivimaki, Mika; Klopp, Norman; Kolovou, Genovefa; Komulainen, Pirjo; Kooner, Jaspal S.; Kosova, Gulum; Krauss, Ronald M.; Kuh, Diana; Kutalik, Zoltan; Kuusisto, Johanna; Kvaløy, Kirsti; Lakka, Timo A.; Lee, Nanette R.; Lee, I. Te; Lee, Wen Jane; Levy, Daniel; Li, Xiaohui; Liang, Kae Woei; Lin, Honghuang; Lin, Li; Lindström, Jaana; Lobbens, Stéphane; Männistö, Satu; Müller, Gabriele; Müller-Nurasyid, Martina; Mach, François; Markus, Hugh S.; Marouli, Eirini; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Menni, Cristina; Metspalu, Andres; Mijatovic, Vladan; Moilanen, Leena; Montasser, May E.; Morris, Andrew D.; Morrison, Alanna C.; Mulas, Antonella; Nagaraja, Ramaiah; Narisu, Narisu; Nikus, Kjell; O'Donnell, Christopher J.; O'Reilly, Paul F.; Ong, Ken K.; Paccaud, Fred; Palmer, Cameron D.; Parsa, Afshin; Pedersen, Nancy L.; Penninx, Brenda W.; Perola, Markus; Peters, Annette; Poulter, Neil; Pramstaller, Peter P.; Psaty, Bruce M.; Quertermous, Thomas; Rao, Dabeeru C.; Rasheed, Asif; Rayner, N. William; Renström, Frida; Rettig, Rainer; Rice, Kenneth M.; Roberts, Robert; Rose, Lynda M.; Rossouw, Jacques; Samani, Nilesh J.; Sanna, Serena; Saramies, Jouko; Schunkert, Heribert; Sebert, Sylvain; Sheu, Wayne H.H.; Shin, Young Ah; Sim, Xueling; Smit, Johannes H.; Smith, Albert V.; Sosa, Maria X.; Spector, Tim D.; Stančáková, Alena; Stanton, Alice V.; Stirrups, Kathleen E.; Stringham, Heather M.; Sundstrom, Johan; Swift, Amy J.; Syvänen, Ann Christine; Tai, E. Shyong; Tanaka, Toshiko; Tarasov, Kirill V.; Teumer, Alexander; Thorsteinsdottir, Unnur; Tobin, Martin D.; Tremoli, Elena; Uitterlinden, Andre G.; Uusitupa, Matti; Vaez, Ahmad; Vaidya, Dhananjay; Van Duijn, Cornelia M.; Van Iperen, Erik P.A.; Vasan, Ramachandran S.; Verwoert, Germaine C.; Virtamo, Jarmo; Vitart, Veronique; Voight, Benjamin F.; Vollenweider, Peter; Wagner, Aline; Wain, Louise V.; Wareham, Nicholas J.; Watkins, Hugh; Weder, Alan B.; Westra, Harm Jan; Wilks, Rainford; Wilsgaard, Tom; Wilson, James F.; Wong, Tien Y.; Yang, Tsun Po; Yao, Jie; Yengo, Loic; Zhang, Weihua; Zhao, Jing Hua; Zhu, Xiaofeng; Bovet, Pascal; Cooper, Richard S.; Mohlke, Karen L.; Saleheen, Danish; Lee, Jong Young; Elliott, Paul; Gierman, Hinco J.; Willer, Cristen J.; Franke, Lude; Hovingh, G. Kees; Taylor, Kent D.; Dedoussis, George; Sever, Peter; Wong, Andrew; Lind, Lars; Assimes, Themistocles L.; Njølstad, Inger; Schwarz, Peter E.H.; Langenberg, Claudia; Snieder, Harold; Caulfield, Mark J.; Melander, Olle; Laakso, Markku; Saltevo, Juha; Rauramaa, Rainer; Tuomilehto, Jaakko; Ingelsson, Erik; Lehtimäki, Terho; Hveem, Kristian; Palmas, Walter; März, Winfried; Kumari, Meena; Salomaa, Veikko; Chen, Yii Der I.; Rotter, Jerome I.; Froguel, Philippe; Jarvelin, Marjo Riitta; Lakatta, Edward G.; Kuulasmaa, Kari; Franks, Paul W.; Hamsten, Anders; Wichmann, H. Erich; Palmer, Colin N.A.; Stefansson, Kari; Ridker, Paul M.; Loos, Ruth J.F.; Chakravarti, Aravinda; Deloukas, Panos; Morris, Andrew P.; Newton-Cheh, Christopher; Munroe, Patricia B.

In: Nature Genetics, Vol. 48, No. 10, 01.10.2016, p. 1171-1184.

Research output: Contribution to journalArticle

Ehret, GB, Ferreira, T, Chasman, DI, Jackson, AU, Schmidt, EM, Johnson, T, Thorleifsson, G, Luan, JA, Donnelly, LA, Kanoni, S, Petersen, AK, Pihur, V, Strawbridge, RJ, Shungin, D, Hughes, MF, Meirelles, O, Kaakinen, M, Bouatia-Naji, N, Kristiansson, K, Shah, S, Kleber, ME, Guo, X, Lyytikäinen, LP, Fava, C, Eriksson, N, Nolte, IM, Magnusson, PK, Salfati, EL, Rallidis, LS, Theusch, E, Smith, AJP, Folkersen, L, Witkowska, K, Pers, TH, Joehanes, R, Kim, SK, Lataniotis, L, Jansen, R, Johnson, AD, Warren, H, Kim, YJ, Zhao, W, Wu, Y, Tayo, BO, Bochud, M, Absher, D, Adair, LS, Amin, N, Arking, DE, Axelsson, T, Baldassarre, D, Balkau, B, Bandinelli, S, Barnes, MR, Barroso, I, Bevan, S, Bis, JC, Bjornsdottir, G, Boehnke, M, Boerwinkle, E, Bonnycastle, LL, Boomsma, DI, Bornstein, SR, Brown, MJ, Burnier, M, Cabrera, CP, Chambers, JC, Chang, IS, Cheng, CY, Chines, PS, Chung, RH, Collins, FS, Connell, JM, Döring, A, Dallongeville, J, Danesh, J, De Faire, U, Delgado, G, Dominiczak, AF, Doney, ASF, Drenos, F, Edkins, S, Eicher, JD, Elosua, R, Enroth, S, Erdmann, J, Eriksson, P, Esko, T, Evangelou, E, Evans, A, Fall, T, Farrall, M, Felix, JF, Ferrières, J, Ferrucci, L, Fornage, M, Forrester, T, Franceschini, N, Franco, OH, Franco-Cereceda, A, Fraser, RM, Ganesh, SK, Gao, H, Gertow, K, Gianfagna, F, Gigante, B, Giulianini, F, Goel, A, Goodall, AH, Goodarzi, MO, Gorski, M, Gräßler, J, Groves, CJ, Gudnason, V, Gyllensten, U, Hallmans, G, Hartikainen, AL, Hassinen, M, Havulinna, AS, Hayward, C, Hercberg, S, Herzig, KH, Hicks, AA, Hingorani, AD, Hirschhorn, JN, Hofman, A, Holmen, J, Holmen, OL, Hottenga, JJ, Howard, P, Hsiung, CA, Hunt, S, Ikram, MA, Illig, T, Iribarren, C, Jensen, RA, Kähönen, M, Kang, HM, Kathiresan, S, Keating, BJ, Khaw, KT, Kim, YK, Kim, E, Kivimaki, M, Klopp, N, Kolovou, G, Komulainen, P, Kooner, JS, Kosova, G, Krauss, RM, Kuh, D, Kutalik, Z, Kuusisto, J, Kvaløy, K, Lakka, TA, Lee, NR, Lee, IT, Lee, WJ, Levy, D, Li, X, Liang, KW, Lin, H, Lin, L, Lindström, J, Lobbens, S, Männistö, S, Müller, G, Müller-Nurasyid, M, Mach, F, Markus, HS, Marouli, E, McCarthy, MI, McKenzie, CA, Meneton, P, Menni, C, Metspalu, A, Mijatovic, V, Moilanen, L, Montasser, ME, Morris, AD, Morrison, AC, Mulas, A, Nagaraja, R, Narisu, N, Nikus, K, O'Donnell, CJ, O'Reilly, PF, Ong, KK, Paccaud, F, Palmer, CD, Parsa, A, Pedersen, NL, Penninx, BW, Perola, M, Peters, A, Poulter, N, Pramstaller, PP, Psaty, BM, Quertermous, T, Rao, DC, Rasheed, A, Rayner, NW, Renström, F, Rettig, R, Rice, KM, Roberts, R, Rose, LM, Rossouw, J, Samani, NJ, Sanna, S, Saramies, J, Schunkert, H, Sebert, S, Sheu, WHH, Shin, YA, Sim, X, Smit, JH, Smith, AV, Sosa, MX, Spector, TD, Stančáková, A, Stanton, AV, Stirrups, KE, Stringham, HM, Sundstrom, J, Swift, AJ, Syvänen, AC, Tai, ES, Tanaka, T, Tarasov, KV, Teumer, A, Thorsteinsdottir, U, Tobin, MD, Tremoli, E, Uitterlinden, AG, Uusitupa, M, Vaez, A, Vaidya, D, Van Duijn, CM, Van Iperen, EPA, Vasan, RS, Verwoert, GC, Virtamo, J, Vitart, V, Voight, BF, Vollenweider, P, Wagner, A, Wain, LV, Wareham, NJ, Watkins, H, Weder, AB, Westra, HJ, Wilks, R, Wilsgaard, T, Wilson, JF, Wong, TY, Yang, TP, Yao, J, Yengo, L, Zhang, W, Zhao, JH, Zhu, X, Bovet, P, Cooper, RS, Mohlke, KL, Saleheen, D, Lee, JY, Elliott, P, Gierman, HJ, Willer, CJ, Franke, L, Hovingh, GK, Taylor, KD, Dedoussis, G, Sever, P, Wong, A, Lind, L, Assimes, TL, Njølstad, I, Schwarz, PEH, Langenberg, C, Snieder, H, Caulfield, MJ, Melander, O, Laakso, M, Saltevo, J, Rauramaa, R, Tuomilehto, J, Ingelsson, E, Lehtimäki, T, Hveem, K, Palmas, W, März, W, Kumari, M, Salomaa, V, Chen, YDI, Rotter, JI, Froguel, P, Jarvelin, MR, Lakatta, EG, Kuulasmaa, K, Franks, PW, Hamsten, A, Wichmann, HE, Palmer, CNA, Stefansson, K, Ridker, PM, Loos, RJF, Chakravarti, A, Deloukas, P, Morris, AP, Newton-Cheh, C & Munroe, PB 2016, 'The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals', Nature Genetics, vol. 48, no. 10, pp. 1171-1184. https://doi.org/10.1038/ng.3667
Ehret GB, Ferreira T, Chasman DI, Jackson AU, Schmidt EM, Johnson T et al. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nature Genetics. 2016 Oct 1;48(10):1171-1184. https://doi.org/10.1038/ng.3667
Ehret, Georg B. ; Ferreira, Teresa ; Chasman, Daniel I. ; Jackson, Anne U. ; Schmidt, Ellen M. ; Johnson, Toby ; Thorleifsson, Gudmar ; Luan, Jian'An ; Donnelly, Louise A. ; Kanoni, Stavroula ; Petersen, Ann Kristin ; Pihur, Vasyl ; Strawbridge, Rona J. ; Shungin, Dmitry ; Hughes, Maria F. ; Meirelles, Osorio ; Kaakinen, Marika ; Bouatia-Naji, Nabila ; Kristiansson, Kati ; Shah, Sonia ; Kleber, Marcus E. ; Guo, Xiuqing ; Lyytikäinen, Leo Pekka ; Fava, Cristiano ; Eriksson, Niclas ; Nolte, Ilja M. ; Magnusson, Patrik K. ; Salfati, Elias L. ; Rallidis, Loukianos S. ; Theusch, Elizabeth ; Smith, Andrew J.P. ; Folkersen, Lasse ; Witkowska, Kate ; Pers, Tune H. ; Joehanes, Roby ; Kim, Stuart K. ; Lataniotis, Lazaros ; Jansen, Rick ; Johnson, Andrew D. ; Warren, Helen ; Kim, Young Jin ; Zhao, Wei ; Wu, Ying ; Tayo, Bamidele O. ; Bochud, Murielle ; Absher, Devin ; Adair, Linda S. ; Amin, Najaf ; Arking, Dan E. ; Axelsson, Tomas ; Baldassarre, Damiano ; Balkau, Beverley ; Bandinelli, Stefania ; Barnes, Michael R. ; Barroso, Inês ; Bevan, Stephen ; Bis, Joshua C. ; Bjornsdottir, Gyda ; Boehnke, Michael ; Boerwinkle, Eric ; Bonnycastle, Lori L. ; Boomsma, Dorret I. ; Bornstein, Stefan R. ; Brown, Morris J. ; Burnier, Michel ; Cabrera, Claudia P. ; Chambers, John C. ; Chang, I. Shou ; Cheng, Ching Yu ; Chines, Peter S. ; Chung, Ren Hua ; Collins, Francis S. ; Connell, John M. ; Döring, Angela ; Dallongeville, Jean ; Danesh, John ; De Faire, Ulf ; Delgado, Graciela ; Dominiczak, Anna F. ; Doney, Alex S.F. ; Drenos, Fotios ; Edkins, Sarah ; Eicher, John D. ; Elosua, Roberto ; Enroth, Stefan ; Erdmann, Jeanette ; Eriksson, Per ; Esko, Tonu ; Evangelou, Evangelos ; Evans, Alun ; Fall, Tove ; Farrall, Martin ; Felix, Janine F. ; Ferrières, Jean ; Ferrucci, Luigi ; Fornage, Myriam ; Forrester, Terrence ; Franceschini, Nora ; Franco, Oscar H. ; Franco-Cereceda, Anders ; Fraser, Ross M. ; Ganesh, Santhi K. ; Gao, He ; Gertow, Karl ; Gianfagna, Francesco ; Gigante, Bruna ; Giulianini, Franco ; Goel, Anuj ; Goodall, Alison H. ; Goodarzi, Mark O. ; Gorski, Mathias ; Gräßler, Jürgen ; Groves, Christopher J. ; Gudnason, Vilmundur ; Gyllensten, Ulf ; Hallmans, Göran ; Hartikainen, Anna Liisa ; Hassinen, Maija ; Havulinna, Aki S. ; Hayward, Caroline ; Hercberg, Serge ; Herzig, Karl Heinz ; Hicks, Andrew A. ; Hingorani, Aroon D. ; Hirschhorn, Joel N. ; Hofman, Albert ; Holmen, Jostein ; Holmen, Oddgeir Lingaas ; Hottenga, Jouke Jan ; Howard, Phil ; Hsiung, Chao A. ; Hunt, Steven ; Ikram, M. Arfan ; Illig, Thomas ; Iribarren, Carlos ; Jensen, Richard A. ; Kähönen, Mika ; Kang, Hyun Min ; Kathiresan, Sekar ; Keating, Brendan J. ; Khaw, Kay Tee ; Kim, Yun Kyoung ; Kim, Eric ; Kivimaki, Mika ; Klopp, Norman ; Kolovou, Genovefa ; Komulainen, Pirjo ; Kooner, Jaspal S. ; Kosova, Gulum ; Krauss, Ronald M. ; Kuh, Diana ; Kutalik, Zoltan ; Kuusisto, Johanna ; Kvaløy, Kirsti ; Lakka, Timo A. ; Lee, Nanette R. ; Lee, I. Te ; Lee, Wen Jane ; Levy, Daniel ; Li, Xiaohui ; Liang, Kae Woei ; Lin, Honghuang ; Lin, Li ; Lindström, Jaana ; Lobbens, Stéphane ; Männistö, Satu ; Müller, Gabriele ; Müller-Nurasyid, Martina ; Mach, François ; Markus, Hugh S. ; Marouli, Eirini ; McCarthy, Mark I. ; McKenzie, Colin A. ; Meneton, Pierre ; Menni, Cristina ; Metspalu, Andres ; Mijatovic, Vladan ; Moilanen, Leena ; Montasser, May E. ; Morris, Andrew D. ; Morrison, Alanna C. ; Mulas, Antonella ; Nagaraja, Ramaiah ; Narisu, Narisu ; Nikus, Kjell ; O'Donnell, Christopher J. ; O'Reilly, Paul F. ; Ong, Ken K. ; Paccaud, Fred ; Palmer, Cameron D. ; Parsa, Afshin ; Pedersen, Nancy L. ; Penninx, Brenda W. ; Perola, Markus ; Peters, Annette ; Poulter, Neil ; Pramstaller, Peter P. ; Psaty, Bruce M. ; Quertermous, Thomas ; Rao, Dabeeru C. ; Rasheed, Asif ; Rayner, N. William ; Renström, Frida ; Rettig, Rainer ; Rice, Kenneth M. ; Roberts, Robert ; Rose, Lynda M. ; Rossouw, Jacques ; Samani, Nilesh J. ; Sanna, Serena ; Saramies, Jouko ; Schunkert, Heribert ; Sebert, Sylvain ; Sheu, Wayne H.H. ; Shin, Young Ah ; Sim, Xueling ; Smit, Johannes H. ; Smith, Albert V. ; Sosa, Maria X. ; Spector, Tim D. ; Stančáková, Alena ; Stanton, Alice V. ; Stirrups, Kathleen E. ; Stringham, Heather M. ; Sundstrom, Johan ; Swift, Amy J. ; Syvänen, Ann Christine ; Tai, E. Shyong ; Tanaka, Toshiko ; Tarasov, Kirill V. ; Teumer, Alexander ; Thorsteinsdottir, Unnur ; Tobin, Martin D. ; Tremoli, Elena ; Uitterlinden, Andre G. ; Uusitupa, Matti ; Vaez, Ahmad ; Vaidya, Dhananjay ; Van Duijn, Cornelia M. ; Van Iperen, Erik P.A. ; Vasan, Ramachandran S. ; Verwoert, Germaine C. ; Virtamo, Jarmo ; Vitart, Veronique ; Voight, Benjamin F. ; Vollenweider, Peter ; Wagner, Aline ; Wain, Louise V. ; Wareham, Nicholas J. ; Watkins, Hugh ; Weder, Alan B. ; Westra, Harm Jan ; Wilks, Rainford ; Wilsgaard, Tom ; Wilson, James F. ; Wong, Tien Y. ; Yang, Tsun Po ; Yao, Jie ; Yengo, Loic ; Zhang, Weihua ; Zhao, Jing Hua ; Zhu, Xiaofeng ; Bovet, Pascal ; Cooper, Richard S. ; Mohlke, Karen L. ; Saleheen, Danish ; Lee, Jong Young ; Elliott, Paul ; Gierman, Hinco J. ; Willer, Cristen J. ; Franke, Lude ; Hovingh, G. Kees ; Taylor, Kent D. ; Dedoussis, George ; Sever, Peter ; Wong, Andrew ; Lind, Lars ; Assimes, Themistocles L. ; Njølstad, Inger ; Schwarz, Peter E.H. ; Langenberg, Claudia ; Snieder, Harold ; Caulfield, Mark J. ; Melander, Olle ; Laakso, Markku ; Saltevo, Juha ; Rauramaa, Rainer ; Tuomilehto, Jaakko ; Ingelsson, Erik ; Lehtimäki, Terho ; Hveem, Kristian ; Palmas, Walter ; März, Winfried ; Kumari, Meena ; Salomaa, Veikko ; Chen, Yii Der I. ; Rotter, Jerome I. ; Froguel, Philippe ; Jarvelin, Marjo Riitta ; Lakatta, Edward G. ; Kuulasmaa, Kari ; Franks, Paul W. ; Hamsten, Anders ; Wichmann, H. Erich ; Palmer, Colin N.A. ; Stefansson, Kari ; Ridker, Paul M. ; Loos, Ruth J.F. ; Chakravarti, Aravinda ; Deloukas, Panos ; Morris, Andrew P. ; Newton-Cheh, Christopher ; Munroe, Patricia B. / The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. In: Nature Genetics. 2016 ; Vol. 48, No. 10. pp. 1171-1184.
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title = "The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals",
abstract = "To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.",
author = "Ehret, {Georg B.} and Teresa Ferreira and Chasman, {Daniel I.} and Jackson, {Anne U.} and Schmidt, {Ellen M.} and Toby Johnson and Gudmar Thorleifsson and Jian'An Luan and Donnelly, {Louise A.} and Stavroula Kanoni and Petersen, {Ann Kristin} and Vasyl Pihur and Strawbridge, {Rona J.} and Dmitry Shungin and Hughes, {Maria F.} and Osorio Meirelles and Marika Kaakinen and Nabila Bouatia-Naji and Kati Kristiansson and Sonia Shah and Kleber, {Marcus E.} and Xiuqing Guo and Lyytik{\"a}inen, {Leo Pekka} and Cristiano Fava and Niclas Eriksson and Nolte, {Ilja M.} and Magnusson, {Patrik K.} and Salfati, {Elias L.} and Rallidis, {Loukianos S.} and Elizabeth Theusch and Smith, {Andrew J.P.} and Lasse Folkersen and Kate Witkowska and Pers, {Tune H.} and Roby Joehanes and Kim, {Stuart K.} and Lazaros Lataniotis and Rick Jansen and Johnson, {Andrew D.} and Helen Warren and Kim, {Young Jin} and Wei Zhao and Ying Wu and Tayo, {Bamidele O.} and Murielle Bochud and Devin Absher and Adair, {Linda S.} and Najaf Amin and Arking, {Dan E.} and Tomas Axelsson and Damiano Baldassarre and Beverley Balkau and Stefania Bandinelli and Barnes, {Michael R.} and In{\^e}s Barroso and Stephen Bevan and Bis, {Joshua C.} and Gyda Bjornsdottir and Michael Boehnke and Eric Boerwinkle and Bonnycastle, {Lori L.} and Boomsma, {Dorret I.} and Bornstein, {Stefan R.} and Brown, {Morris J.} and Michel Burnier and Cabrera, {Claudia P.} and Chambers, {John C.} and Chang, {I. Shou} and Cheng, {Ching Yu} and Chines, {Peter S.} and Chung, {Ren Hua} and Collins, {Francis S.} and Connell, {John M.} and Angela D{\"o}ring and Jean Dallongeville and John Danesh and {De Faire}, Ulf and Graciela Delgado and Dominiczak, {Anna F.} and Doney, {Alex S.F.} and Fotios Drenos and Sarah Edkins and Eicher, {John D.} and Roberto Elosua and Stefan Enroth and Jeanette Erdmann and Per Eriksson and Tonu Esko and Evangelos Evangelou and Alun Evans and Tove Fall and Martin Farrall and Felix, {Janine F.} and Jean Ferri{\`e}res and Luigi Ferrucci and Myriam Fornage and Terrence Forrester and Nora Franceschini and Franco, {Oscar H.} and Anders Franco-Cereceda and Fraser, {Ross M.} and Ganesh, {Santhi K.} and He Gao and Karl Gertow and Francesco Gianfagna and Bruna Gigante and Franco Giulianini and Anuj Goel and Goodall, {Alison H.} and Goodarzi, {Mark O.} and Mathias Gorski and J{\"u}rgen Gr{\"a}{\ss}ler and Groves, {Christopher J.} and Vilmundur Gudnason and Ulf Gyllensten and G{\"o}ran Hallmans and Hartikainen, {Anna Liisa} and Maija Hassinen and Havulinna, {Aki S.} and Caroline Hayward and Serge Hercberg and Herzig, {Karl Heinz} and Hicks, {Andrew A.} and Hingorani, {Aroon D.} and Hirschhorn, {Joel N.} and Albert Hofman and Jostein Holmen and Holmen, {Oddgeir Lingaas} and Hottenga, {Jouke Jan} and Phil Howard and Hsiung, {Chao A.} and Steven Hunt and Ikram, {M. Arfan} and Thomas Illig and Carlos Iribarren and Jensen, {Richard A.} and Mika K{\"a}h{\"o}nen and Kang, {Hyun Min} and Sekar Kathiresan and Keating, {Brendan J.} and Khaw, {Kay Tee} and Kim, {Yun Kyoung} and Eric Kim and Mika Kivimaki and Norman Klopp and Genovefa Kolovou and Pirjo Komulainen and Kooner, {Jaspal S.} and Gulum Kosova and Krauss, {Ronald M.} and Diana Kuh and Zoltan Kutalik and Johanna Kuusisto and Kirsti Kval{\o}y and Lakka, {Timo A.} and Lee, {Nanette R.} and Lee, {I. Te} and Lee, {Wen Jane} and Daniel Levy and Xiaohui Li and Liang, {Kae Woei} and Honghuang Lin and Li Lin and Jaana Lindstr{\"o}m and St{\'e}phane Lobbens and Satu M{\"a}nnist{\"o} and Gabriele M{\"u}ller and Martina M{\"u}ller-Nurasyid and Fran{\cc}ois Mach and Markus, {Hugh S.} and Eirini Marouli and McCarthy, {Mark I.} and McKenzie, {Colin A.} and Pierre Meneton and Cristina Menni and Andres Metspalu and Vladan Mijatovic and Leena Moilanen and Montasser, {May E.} and Morris, {Andrew D.} and Morrison, {Alanna C.} and Antonella Mulas and Ramaiah Nagaraja and Narisu Narisu and Kjell Nikus and O'Donnell, {Christopher J.} and O'Reilly, {Paul F.} and Ong, {Ken K.} and Fred Paccaud and Palmer, {Cameron D.} and Afshin Parsa and Pedersen, {Nancy L.} and Penninx, {Brenda W.} and Markus Perola and Annette Peters and Neil Poulter and Pramstaller, {Peter P.} and Psaty, {Bruce M.} and Thomas Quertermous and Rao, {Dabeeru C.} and Asif Rasheed and Rayner, {N. William} and Frida Renstr{\"o}m and Rainer Rettig and Rice, {Kenneth M.} and Robert Roberts and Rose, {Lynda M.} and Jacques Rossouw and Samani, {Nilesh J.} and Serena Sanna and Jouko Saramies and Heribert Schunkert and Sylvain Sebert and Sheu, {Wayne H.H.} and Shin, {Young Ah} and Xueling Sim and Smit, {Johannes H.} and Smith, {Albert V.} and Sosa, {Maria X.} and Spector, {Tim D.} and Alena Stanč{\'a}kov{\'a} and Stanton, {Alice V.} and Stirrups, {Kathleen E.} and Stringham, {Heather M.} and Johan Sundstrom and Swift, {Amy J.} and Syv{\"a}nen, {Ann Christine} and Tai, {E. Shyong} and Toshiko Tanaka and Tarasov, {Kirill V.} and Alexander Teumer and Unnur Thorsteinsdottir and Tobin, {Martin D.} and Elena Tremoli and Uitterlinden, {Andre G.} and Matti Uusitupa and Ahmad Vaez and Dhananjay Vaidya and {Van Duijn}, {Cornelia M.} and {Van Iperen}, {Erik P.A.} and Vasan, {Ramachandran S.} and Verwoert, {Germaine C.} and Jarmo Virtamo and Veronique Vitart and Voight, {Benjamin F.} and Peter Vollenweider and Aline Wagner and Wain, {Louise V.} and Wareham, {Nicholas J.} and Hugh Watkins and Weder, {Alan B.} and Westra, {Harm Jan} and Rainford Wilks and Tom Wilsgaard and Wilson, {James F.} and Wong, {Tien Y.} and Yang, {Tsun Po} and Jie Yao and Loic Yengo and Weihua Zhang and Zhao, {Jing Hua} and Xiaofeng Zhu and Pascal Bovet and Cooper, {Richard S.} and Mohlke, {Karen L.} and Danish Saleheen and Lee, {Jong Young} and Paul Elliott and Gierman, {Hinco J.} and Willer, {Cristen J.} and Lude Franke and Hovingh, {G. Kees} and Taylor, {Kent D.} and George Dedoussis and Peter Sever and Andrew Wong and Lars Lind and Assimes, {Themistocles L.} and Inger Nj{\o}lstad and Schwarz, {Peter E.H.} and Claudia Langenberg and Harold Snieder and Caulfield, {Mark J.} and Olle Melander and Markku Laakso and Juha Saltevo and Rainer Rauramaa and Jaakko Tuomilehto and Erik Ingelsson and Terho Lehtim{\"a}ki and Kristian Hveem and Walter Palmas and Winfried M{\"a}rz and Meena Kumari and Veikko Salomaa and Chen, {Yii Der I.} and Rotter, {Jerome I.} and Philippe Froguel and Jarvelin, {Marjo Riitta} and Lakatta, {Edward G.} and Kari Kuulasmaa and Franks, {Paul W.} and Anders Hamsten and Wichmann, {H. Erich} and Palmer, {Colin N.A.} and Kari Stefansson and Ridker, {Paul M.} and Loos, {Ruth J.F.} and Aravinda Chakravarti and Panos Deloukas and Morris, {Andrew P.} and Christopher Newton-Cheh and Munroe, {Patricia B.}",
year = "2016",
month = "10",
day = "1",
doi = "10.1038/ng.3667",
language = "English",
volume = "48",
pages = "1171--1184",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

AU - Ehret, Georg B.

AU - Ferreira, Teresa

AU - Chasman, Daniel I.

AU - Jackson, Anne U.

AU - Schmidt, Ellen M.

AU - Johnson, Toby

AU - Thorleifsson, Gudmar

AU - Luan, Jian'An

AU - Donnelly, Louise A.

AU - Kanoni, Stavroula

AU - Petersen, Ann Kristin

AU - Pihur, Vasyl

AU - Strawbridge, Rona J.

AU - Shungin, Dmitry

AU - Hughes, Maria F.

AU - Meirelles, Osorio

AU - Kaakinen, Marika

AU - Bouatia-Naji, Nabila

AU - Kristiansson, Kati

AU - Shah, Sonia

AU - Kleber, Marcus E.

AU - Guo, Xiuqing

AU - Lyytikäinen, Leo Pekka

AU - Fava, Cristiano

AU - Eriksson, Niclas

AU - Nolte, Ilja M.

AU - Magnusson, Patrik K.

AU - Salfati, Elias L.

AU - Rallidis, Loukianos S.

AU - Theusch, Elizabeth

AU - Smith, Andrew J.P.

AU - Folkersen, Lasse

AU - Witkowska, Kate

AU - Pers, Tune H.

AU - Joehanes, Roby

AU - Kim, Stuart K.

AU - Lataniotis, Lazaros

AU - Jansen, Rick

AU - Johnson, Andrew D.

AU - Warren, Helen

AU - Kim, Young Jin

AU - Zhao, Wei

AU - Wu, Ying

AU - Tayo, Bamidele O.

AU - Bochud, Murielle

AU - Absher, Devin

AU - Adair, Linda S.

AU - Amin, Najaf

AU - Arking, Dan E.

AU - Axelsson, Tomas

AU - Baldassarre, Damiano

AU - Balkau, Beverley

AU - Bandinelli, Stefania

AU - Barnes, Michael R.

AU - Barroso, Inês

AU - Bevan, Stephen

AU - Bis, Joshua C.

AU - Bjornsdottir, Gyda

AU - Boehnke, Michael

AU - Boerwinkle, Eric

AU - Bonnycastle, Lori L.

AU - Boomsma, Dorret I.

AU - Bornstein, Stefan R.

AU - Brown, Morris J.

AU - Burnier, Michel

AU - Cabrera, Claudia P.

AU - Chambers, John C.

AU - Chang, I. Shou

AU - Cheng, Ching Yu

AU - Chines, Peter S.

AU - Chung, Ren Hua

AU - Collins, Francis S.

AU - Connell, John M.

AU - Döring, Angela

AU - Dallongeville, Jean

AU - Danesh, John

AU - De Faire, Ulf

AU - Delgado, Graciela

AU - Dominiczak, Anna F.

AU - Doney, Alex S.F.

AU - Drenos, Fotios

AU - Edkins, Sarah

AU - Eicher, John D.

AU - Elosua, Roberto

AU - Enroth, Stefan

AU - Erdmann, Jeanette

AU - Eriksson, Per

AU - Esko, Tonu

AU - Evangelou, Evangelos

AU - Evans, Alun

AU - Fall, Tove

AU - Farrall, Martin

AU - Felix, Janine F.

AU - Ferrières, Jean

AU - Ferrucci, Luigi

AU - Fornage, Myriam

AU - Forrester, Terrence

AU - Franceschini, Nora

AU - Franco, Oscar H.

AU - Franco-Cereceda, Anders

AU - Fraser, Ross M.

AU - Ganesh, Santhi K.

AU - Gao, He

AU - Gertow, Karl

AU - Gianfagna, Francesco

AU - Gigante, Bruna

AU - Giulianini, Franco

AU - Goel, Anuj

AU - Goodall, Alison H.

AU - Goodarzi, Mark O.

AU - Gorski, Mathias

AU - Gräßler, Jürgen

AU - Groves, Christopher J.

AU - Gudnason, Vilmundur

AU - Gyllensten, Ulf

AU - Hallmans, Göran

AU - Hartikainen, Anna Liisa

AU - Hassinen, Maija

AU - Havulinna, Aki S.

AU - Hayward, Caroline

AU - Hercberg, Serge

AU - Herzig, Karl Heinz

AU - Hicks, Andrew A.

AU - Hingorani, Aroon D.

AU - Hirschhorn, Joel N.

AU - Hofman, Albert

AU - Holmen, Jostein

AU - Holmen, Oddgeir Lingaas

AU - Hottenga, Jouke Jan

AU - Howard, Phil

AU - Hsiung, Chao A.

AU - Hunt, Steven

AU - Ikram, M. Arfan

AU - Illig, Thomas

AU - Iribarren, Carlos

AU - Jensen, Richard A.

AU - Kähönen, Mika

AU - Kang, Hyun Min

AU - Kathiresan, Sekar

AU - Keating, Brendan J.

AU - Khaw, Kay Tee

AU - Kim, Yun Kyoung

AU - Kim, Eric

AU - Kivimaki, Mika

AU - Klopp, Norman

AU - Kolovou, Genovefa

AU - Komulainen, Pirjo

AU - Kooner, Jaspal S.

AU - Kosova, Gulum

AU - Krauss, Ronald M.

AU - Kuh, Diana

AU - Kutalik, Zoltan

AU - Kuusisto, Johanna

AU - Kvaløy, Kirsti

AU - Lakka, Timo A.

AU - Lee, Nanette R.

AU - Lee, I. Te

AU - Lee, Wen Jane

AU - Levy, Daniel

AU - Li, Xiaohui

AU - Liang, Kae Woei

AU - Lin, Honghuang

AU - Lin, Li

AU - Lindström, Jaana

AU - Lobbens, Stéphane

AU - Männistö, Satu

AU - Müller, Gabriele

AU - Müller-Nurasyid, Martina

AU - Mach, François

AU - Markus, Hugh S.

AU - Marouli, Eirini

AU - McCarthy, Mark I.

AU - McKenzie, Colin A.

AU - Meneton, Pierre

AU - Menni, Cristina

AU - Metspalu, Andres

AU - Mijatovic, Vladan

AU - Moilanen, Leena

AU - Montasser, May E.

AU - Morris, Andrew D.

AU - Morrison, Alanna C.

AU - Mulas, Antonella

AU - Nagaraja, Ramaiah

AU - Narisu, Narisu

AU - Nikus, Kjell

AU - O'Donnell, Christopher J.

AU - O'Reilly, Paul F.

AU - Ong, Ken K.

AU - Paccaud, Fred

AU - Palmer, Cameron D.

AU - Parsa, Afshin

AU - Pedersen, Nancy L.

AU - Penninx, Brenda W.

AU - Perola, Markus

AU - Peters, Annette

AU - Poulter, Neil

AU - Pramstaller, Peter P.

AU - Psaty, Bruce M.

AU - Quertermous, Thomas

AU - Rao, Dabeeru C.

AU - Rasheed, Asif

AU - Rayner, N. William

AU - Renström, Frida

AU - Rettig, Rainer

AU - Rice, Kenneth M.

AU - Roberts, Robert

AU - Rose, Lynda M.

AU - Rossouw, Jacques

AU - Samani, Nilesh J.

AU - Sanna, Serena

AU - Saramies, Jouko

AU - Schunkert, Heribert

AU - Sebert, Sylvain

AU - Sheu, Wayne H.H.

AU - Shin, Young Ah

AU - Sim, Xueling

AU - Smit, Johannes H.

AU - Smith, Albert V.

AU - Sosa, Maria X.

AU - Spector, Tim D.

AU - Stančáková, Alena

AU - Stanton, Alice V.

AU - Stirrups, Kathleen E.

AU - Stringham, Heather M.

AU - Sundstrom, Johan

AU - Swift, Amy J.

AU - Syvänen, Ann Christine

AU - Tai, E. Shyong

AU - Tanaka, Toshiko

AU - Tarasov, Kirill V.

AU - Teumer, Alexander

AU - Thorsteinsdottir, Unnur

AU - Tobin, Martin D.

AU - Tremoli, Elena

AU - Uitterlinden, Andre G.

AU - Uusitupa, Matti

AU - Vaez, Ahmad

AU - Vaidya, Dhananjay

AU - Van Duijn, Cornelia M.

AU - Van Iperen, Erik P.A.

AU - Vasan, Ramachandran S.

AU - Verwoert, Germaine C.

AU - Virtamo, Jarmo

AU - Vitart, Veronique

AU - Voight, Benjamin F.

AU - Vollenweider, Peter

AU - Wagner, Aline

AU - Wain, Louise V.

AU - Wareham, Nicholas J.

AU - Watkins, Hugh

AU - Weder, Alan B.

AU - Westra, Harm Jan

AU - Wilks, Rainford

AU - Wilsgaard, Tom

AU - Wilson, James F.

AU - Wong, Tien Y.

AU - Yang, Tsun Po

AU - Yao, Jie

AU - Yengo, Loic

AU - Zhang, Weihua

AU - Zhao, Jing Hua

AU - Zhu, Xiaofeng

AU - Bovet, Pascal

AU - Cooper, Richard S.

AU - Mohlke, Karen L.

AU - Saleheen, Danish

AU - Lee, Jong Young

AU - Elliott, Paul

AU - Gierman, Hinco J.

AU - Willer, Cristen J.

AU - Franke, Lude

AU - Hovingh, G. Kees

AU - Taylor, Kent D.

AU - Dedoussis, George

AU - Sever, Peter

AU - Wong, Andrew

AU - Lind, Lars

AU - Assimes, Themistocles L.

AU - Njølstad, Inger

AU - Schwarz, Peter E.H.

AU - Langenberg, Claudia

AU - Snieder, Harold

AU - Caulfield, Mark J.

AU - Melander, Olle

AU - Laakso, Markku

AU - Saltevo, Juha

AU - Rauramaa, Rainer

AU - Tuomilehto, Jaakko

AU - Ingelsson, Erik

AU - Lehtimäki, Terho

AU - Hveem, Kristian

AU - Palmas, Walter

AU - März, Winfried

AU - Kumari, Meena

AU - Salomaa, Veikko

AU - Chen, Yii Der I.

AU - Rotter, Jerome I.

AU - Froguel, Philippe

AU - Jarvelin, Marjo Riitta

AU - Lakatta, Edward G.

AU - Kuulasmaa, Kari

AU - Franks, Paul W.

AU - Hamsten, Anders

AU - Wichmann, H. Erich

AU - Palmer, Colin N.A.

AU - Stefansson, Kari

AU - Ridker, Paul M.

AU - Loos, Ruth J.F.

AU - Chakravarti, Aravinda

AU - Deloukas, Panos

AU - Morris, Andrew P.

AU - Newton-Cheh, Christopher

AU - Munroe, Patricia B.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

AB - To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

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UR - http://www.scopus.com/inward/citedby.url?scp=84987625495&partnerID=8YFLogxK

U2 - 10.1038/ng.3667

DO - 10.1038/ng.3667

M3 - Article

VL - 48

SP - 1171

EP - 1184

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 10

ER -