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The Genetics of Blood Pressure Regulation and Its Target Organs from Association Studies in 342,415 Individuals

Citation

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, et al. (2016). The Genetics of Blood Pressure Regulation and Its Target Organs from Association Studies in 342,415 Individuals. Nature Genetics, 48(10), 1171-1184. PMCID: PMC5042863

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.

URL

http://dx.doi.org/10.1038/ng.3667

Reference Type

Journal Article

Year Published

2016

Journal Title

Nature Genetics

Author(s)

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
Pihurl, 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
Lyytikainen, Leo-Pekka
Fava, Cristiano
Eriksson, Nidas
Nolte, Ilja M.
Magnusson, Patrik K. E.
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 R.
Kim, Young Jin
Zhao, Wei
Wu, Ying
Tayo, Bamidele O.
Bochud, Murielle
Absher, Devin M.
Adair, Linda S.
Amin, Najaf
Arking, Dan E.
Axelsson, Tomas
Baldassarre, Damiano
Balkau, Beverley
Bandinelli, Stefania
Barnes, Michael R.
Barroso, Ines
Bevan, Stephen
Bis, Joshua C.
Bjornsdottir, Gyda
Boehnke, Michael
Boerwinkle, Eric A.
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.
Doring, Angela
Dallongeville, Jean
Danesh, John
de Faire, Ulf
Delgado, Graciela E.
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
Fai, Tove
Farrall, Martin
Felix, Janine F.
Ferrieres, 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
Grassler, Jurgen
Groves, Christopher J.
Gudnason, Vilmundur G.
Gyllensten, Ulf
Hallmans, Goran
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 L.
Hottenga, Jouke-Jan
Howard, Phil
Hsiung, Chao A.
Hunt, Steven C.
Ikram, M. Arfan
Illig, Thomas
Iribarren, Carlos
Jensen, Richard A.
Kahonen, 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 Singh S.
Kosova, Gulum
Krauss, Ronald M.
Kuh, Diana
Kutalik, Zoltan
Kuusisto, Johanna
Kvaloy, Kirsti
Lakka, Timo A.
Lee, Nanette R.
Lee, I-Te
Lee, Wen-Jane
Levy, Daniel
Li, Xiaohui
Liang, Kae-Woei
Lin, Honghuang
Lin, Li
Lindstrom, Jaana
Lobbens, Stephane
Mannisto, Satu
Muller, Gabriele
Muller-Nurasyid, Martina
Mach, Francois
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. J. H. W.
Perola, Markus
Peters, Annette
Poulter, Neil
Pramstaller, Peter P.
Psaty, Bruce M.
Quertermous, Thomas
Rao, Dabeeru C.
Rasheed, Asif
Rayner, Nigel W.
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 Huey-Herng
Shin, Young-Ah
Sim, Xueling
Smit, Johannes H.
Smith, Albert V.
Sosa, Maria X.
Spector, Timothy D.
Stancakova, Alena
Stanton, Alice V.
Stirrups, Kathleen E.
Stringham, Heather M.
Sundstrom, Johan
Swift, Amy J.
Syvanen, 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 J.
Wilsgaard, Tom
Wilson, James F.
Wong, Tien Yin
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.
Njolstad, Inger
Schwarz, Peter E. H.
Langenberg, Claudia
Snieder, Harold
Caulfield, Mark J.
Melander, Olle
Laakso, Markku
Saltevo, Juha
Rauramaa, Rainer
Tuomilehto, Jaakko
Ingelsson, Erik
Lehtimaki, Terho
Hveem, Kristian
Palmas, Walter
Marz, Winfried
Kumari, Meena
Salomaa, Veikko
Chen, Yii-Der Ida
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 H.
Munroe, Patricia B.

PMCID

PMC5042863