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

Publication

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

Journal Paper/Review - Sep 12, 2016

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

Citation

Tremoli E, Sebert S, Schunkert H, Saramies J, Sanna S, Samani N, Rossouw J, Rose L, Roberts R, Rice K, Rettig R, Renström F, Rayner N, Rasheed A, Rao D, Quertermous T, Psaty B, Pramstaller P, Sheu W, Shin Y, Sim X, Tobin M, Thorsteinsdottir U, Teumer A, Tarasov K, Tanaka T, Tai E, Syvänen A, Swift A, Sundstrom J, Stringham H, Stirrups K, Stanton A, Stančáková A, Spector T, Sosa M, Smith A, Smit J, Poulter N, Peters A, Meneton P, McKenzie C, McCarthy M, Marouli E, Markus H, Mach F, Müller-Nurasyid M, Müller G, Männistö S, Lobbens S, Lindström J, Lin L, Lin H, Liang K, Li X, Levy D, Lee W, Menni C, Metspalu A, Mijatovic V, Perola M, Penninx B, Pedersen N, Parsa A, Palmer C, Paccaud F, Ong K, O'Reilly P, O'Donnell C, Nikus K, Narisu N, Nagaraja R, Mulas A, Morrison A, Morris A, Montasser M, Moilanen L, Lee I, Uitterlinden A, Munroe P, Palmas W, Hveem K, Lehtimäki T, Ingelsson E, Tuomilehto J, Rauramaa R, Saltevo J, Laakso M, Melander O, Caulfield M, Snieder H, Langenberg C, Schwarz P, Njølstad I, Assimes T, Lind L, Wong A, März W, Kumari M, Salomaa V, Newton-Cheh C, Morris A, Deloukas P, Chakravarti A, Loos R, Ridker P, Stefansson K, Palmer C, Wichmann H, Hamsten A, Franks P, Kuulasmaa K, Lakatta E, Jarvelin M, Froguel P, Rotter J, Chen Y, Sever P, Dedoussis G, Wilks R, Westra H, Weder A, Watkins H, Wareham N, Wain L, Wagner A, Vollenweider P, Voight B, Vitart V, Virtamo J, Verwoert G, Vasan R, van Iperen E, van Duijn C, Vaidya D, Vaez A, Wilsgaard T, Wilson J, Wong T, Taylor K, Hovingh G, Franke L, Willer C, Gierman H, Elliott P, Lee J, Saleheen D, Mohlke K, Cooper R, Bovet P, Zhu X, Zhao J, Zhang W, Yengo L, Yao J, Yang T, Uusitupa M, de Faire U, Bevan S, Barroso I, Barnes M, Bandinelli S, Balkau B, Baldassarre D, Axelsson T, Arking D, Amin N, Adair L, Absher D, Bochud M, Tayo B, Wu Y, Zhao W, Kim Y, Bis J, Bjornsdottir G, Boehnke M, Danesh J, Dallongeville J, Döring A, Connell J, Collins F, Chung R, Chines P, Cheng C, Chang I, Chambers J, Cabrera C, Burnier M, Brown M, Bornstein S, Boomsma D, Bonnycastle L, Boerwinkle E, Warren H, Johnson A, Bouatia-Naji N, Kaakinen M, Meirelles O, Hughes M, Shungin D, Strawbridge R, Pihur V, Petersen A, Kanoni S, Donnelly L, Luan J, Thorleifsson G, Johnson T, Schmidt E, Jackson A, Chasman D, Ferreira T, Kristiansson K, Shah S, Kleber M, Jansen R, Lataniotis L, Kim S, Joehanes R, Pers T, Witkowska K, Folkersen L, Smith A, Theusch E, Rallidis L, Salfati E, Magnusson P, Nolte I, Eriksson N, Fava C, Lyytikäinen L, Guo X, Ehret G, Delgado G, Lee N, Iribarren C, Illig T, Ikram M, Hunt S, Hsiung C, Howard P, Hottenga J, Holmen O, Holmen J, Hofman A, Hirschhorn J, Hingorani A, Hicks A, Herzig K, Hercberg S, Hayward C, Havulinna A, Jensen R, Kähönen M, Kang H, Lakka T, Kvaløy K, Kuusisto J, Kutalik Z, Kuh D, Krauss R, Kosova G, Kooner J, Komulainen P, Kolovou G, Klopp N, Kivimäki M, Kim E, Kim Y, Khaw K, Keating B, Kathiresan S, Hassinen M, Hartikainen A, Fornage M, Ferrucci L, Ferrieres J, Felix J, Farrall M, Fall T, Evans A, Evangelou E, Esko T, Eriksson P, Erdmann J, Enroth S, Elosua R, Eicher J, Edkins S, Drenos F, Doney A, Forrester T, Franceschini N, Duran O, Hallmans G, Gyllensten U, Gudnason V, Groves C, Gräßler J, Gorski M, Goodarzi M, Goodall A, Goel A, Giulianini F, Gigante B, Gianfagna F, Gertow K, Gao H, Ganesh S, Fraser R, Franco-Cereceda A, Dominiczak A. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nat Genet 2016; 48:1171-1184.

Type

Journal Paper/Review (English)

Journal

Nat Genet 2016; 48

Publication Date

Sep 12, 2016

Issn Electronic

1546-1718

Pages

1171-1184

Brief description/objective

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.